Sodium cyanoborohydride → HCID 86683765, compound

HRID 1843255Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][C:18]3([CH3:24])[CH3:23])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[O:25]1[CH2:28][C:27](=O)[CH2:26]1.[BH3-]C#N.[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH:27]4[CH2:28][O:25][CH2:26]4)[CH2:19][C:18]3([CH3:24])[CH3:23])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 125d (900 mg, 2.3 mmol), oxetan-3-one (497 mg, 6.9 mmol), NaBH3CN (435 mg, 6.9 mmol), and zinc chloride (311 mg, 2.3 mmol) in methanol (30 mL) was stirred at 50° C. for 4 hours. It was then concentrated under reduced pressure. water (10 mL) was added to the residue and the mixture was extracted with CHCl3 3×50 mL). The combined organic layer was concentrated under reduced pressure. The residue was purified by silica-gel column-chromatography eluting with 50:1 dichloromethane/methanol to afford 125e (800 mg, 78%). LCMS: [M+H]+ 448.1. 1H NMR (500 MHz, CDCl3) δ 8.65 (d, J=2.0 Hz, 1H), 8.11 (d, J=2.5 Hz, 1H), 7.85 (s, 1H), 7.37-7.34 (m, 1H), 6.96 (d, J=2.5 Hz, 1H), 6.72 (d, J=8.5 Hz, 1H), 4.69-4.61 (m, 4H), 3.60 (s, 3H), 3.50-3.14 (m, 3H), 2.43-2.17 (m, 4H), 1.06 (s, 6H).

Workup

concentrationIt was then concentrated under reduced pressure
additionwater (10 mL) was added to the residue
extractionthe mixture was extracted with CHCl3 3×50 mL)
concentrationThe combined organic layer was concentrated under reduced pressure
customThe residue was purified by silica-gel column-chromatography
washeluting with 50:1 dichloromethane/methanol

Sources & evidence

ORD record: ord-f1e7933a9d57431d8af7bc410639284e
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946213B2

Reaction notes

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