Postmodification of voxelotor (GBT 440) via [Rh]-catalyzed cross dehydrogenative coupling with olefins

Kalshetti, Rupali G.; Rajput, Raveena; Motiwala, Zenia; Reddy, D. Srinivasa; Kulkarni, Kiran; Ramana, Chepuri V.

doi:10.1016/j.bmcl.2022.129022

Cited by 2 publications

(11 citation statements)

References 65 publications

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“…6 Hz,1 H),3 H), 7.30 (t, J = 7. 6 Hz, 2 H), 7.23-7.17 (m, 1 H), 6.95-6.88 (d, J = 16.0 Hz, 1 H), 6.88-6.81 (d, J = 16.8 Hz, 1 H), 4.86 (septet, J = 6.6 Hz, 1 H), 1.50 (d, J = 6.1 Hz, 6 H). 13 C NMR (100 MHz, CDCl 3 ):  = 150.1 (d), 149.6 (s), 138.4 (s), 137.7 (s), 136.6 (d), 135.8 (d), 128.5 (d, 2 C), 127.7 (d), 126.9 (d), 125.9 (d, 2 C), 125.7 (d), 122.9 (d)…”

Section: Special Topic Synthesisunclassified

“…1 H NMR (400 MHz, CDCl 3 ):  = 8.80 (d, J = 3.8 Hz, 1 H), 7.87-7.79 (m, 2 H), 7.45 (d, J = 7. 6 Hz, 1 H), 7.38-7.28 (m, 3 H), 6.89-6.82 (m, J = 16.02 Hz, 3 H), 6.74-6.66 (d, J = 16.0 Hz, 1 H), 4.86 (septet, J = 6.6 Hz, 1 H), 3.80 (s, 3 H), 1.49 (d, J = 6.1 Hz, 6 H). 13 C NMR (100 MHz, CDCl 3 ):  = 158.8 (s), 150.1 (d), 149.7 (s), 138.0 (s), 136.6 (d), 135.6 (d), 130.6 (s), 127.3 (d), 127.1 (d, 2 C), 125.6 (d), 122.8 (d), 119.5 (s), 116.5 (d), 114.0 (d, 2 C), 55.3 (d), 50.6 (q), 22.6 (q, 2 C).…”

Section: (E)-2-(1-isopropyl-4-(4-methoxystyryl)-1h-pyrazol-5-yl)pyrid...mentioning

confidence: 99%

“…6 Hz, 1 H), 7.36 (dd, J = 5.3, 6.9 Hz, 1 H), 7.14-7.07 (t, 1 H), 6.87 (d, J = 7. 6 Hz, 1 H), 6.81-6.76 (d, J = 16.7 Hz, 2 H), 6.75-6.69 (d, J = 16 Hz, 1 H), 6.66 (dd, J = 2.3, 7. 6 Hz, 1 H), 4.83-4.69 (septet, J = 6.8 Hz, 1 H), 1.45 (d, J = 6.9 Hz, 6 H), 1.23 (s, 1 H).…”

Section: (E)-3-(2-(1-isopropyl-5-(pyridin-2-yl)-1h-pyrazol-4-yl)vinyl...mentioning

confidence: 99%

“…6 Hz, 1 H), 6.81-6.76 (d, J = 16.7 Hz, 2 H), 6.75-6.69 (d, J = 16 Hz, 1 H), 6.66 (dd, J = 2.3, 7. 6 Hz, 1 H), 4.83-4.69 (septet, J = 6.8 Hz, 1 H), 1.45 (d, J = 6.9 Hz, 6 H), 1.23 (s, 1 H). 13 C NMR (100 MHz, CDCl 3 ):  = 156.4 (s), 150.0 (d), 149.2 (s), 139.2 (s), 138.3 (s), 137.0 (d), 135.8 (d), 129.6 (d), 127.9 (d), 125.9 (d), 123.2 (d), 119.4 (s), 118.4 (d), 118.3 (d), 114.4 (d), 112.7 (d), 50.9 (d), 22.6 (q, 2 C).…”

Section: (E)-3-(2-(1-isopropyl-5-(pyridin-2-yl)-1h-pyrazol-4-yl)vinyl...unclassified

“…Recently, we have documented the cross dehydrogenative coupling of GBT-440 with various styrenes and have tested them for their anti-sickling activity. 6 However, prior to this, a great deal of work was carried out with the basic scaffold 1 , which has aided the direct functionalization of GBT-440. 7 Herein, we document the same and show that it has led to the synthesis of a large set of diverse derivatives of the pyrazole pyridine scaffold by selective C–H functionalization of the pyrazole unit present in 1 .…”

Section: Table 1 Optimization Studies Amentioning

confidence: 99%

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Rh-Catalyzed C–H Functionalization of the (Pyrazol-5-yl)pyridine Core of GBT-440

2023

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The Rh-catalyzed cross dehydrogenative coupling (CDC)/alkylation of the pyrazolylpyridine unit of the GBT-440 proceeded smoothly at ambient conditions and selectively on the pyrazole unit while being directed by the pyridine. The scope of these reactions has been established by employing simple as well as conjugated olefins for CDC and various diazoesters and the TIPS-EBX reagent for alkylation. At the outset, a focused small molecule library around the bis-heterocyclic core of GBT-440 has been developed via C-H functionalization.

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Section: Special Topic Synthesisunclassified

Section: (E)-2-(1-isopropyl-4-(4-methoxystyryl)-1h-pyrazol-5-yl)pyrid...mentioning

confidence: 99%

Section: (E)-3-(2-(1-isopropyl-5-(pyridin-2-yl)-1h-pyrazol-4-yl)vinyl...mentioning

confidence: 99%

Section: (E)-3-(2-(1-isopropyl-5-(pyridin-2-yl)-1h-pyrazol-4-yl)vinyl...unclassified

Section: Table 1 Optimization Studies Amentioning

confidence: 99%

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Rh-Catalyzed C–H Functionalization of the (Pyrazol-5-yl)pyridine Core of GBT-440

2023

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Concise approach for the synthesis of Voxelotor for sickle cell disease

Manda,

Subba Reddy

2024

Tetrahedron

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Postmodification of voxelotor (GBT 440) via [Rh]-catalyzed cross dehydrogenative coupling with olefins

Cited by 2 publications

References 65 publications

Rh-Catalyzed C–H Functionalization of the (Pyrazol-5-yl)pyridine Core of GBT-440

Rh-Catalyzed C–H Functionalization of the (Pyrazol-5-yl)pyridine Core of GBT-440

Concise approach for the synthesis of Voxelotor for sickle cell disease

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