Sodium borohydride → 8-(3,5-Dimethylisoxazol-4-yl)-6-fluoro-3-pyridin-3-yl-3, 4-dihydro-2H-1,4-benzoxazin-5-amine

HRID 928556Notes

Reaction equation

[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]([F:24])[C:10]([NH2:23])=[C:11]3[C:16]=2[O:15][CH2:14][C:13]([C:17]2[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=2)=[N:12]3)=[C:5]([CH3:25])[O:4][N:3]=1.[BH4-].[Na+]>C(O)C.O>[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]([F:24])[C:10]([NH2:23])=[C:11]3[C:16]=2[O:15][CH2:14][CH:13]([C:17]2[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=2)[NH:12]3)=[C:5]([CH3:25])[O:4][N:3]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 8-(3,5-dimethylisoxazol-4-yl)-6-fluoro-3-pyridin-3-yl-2H-1,4-benzoxazin-5-amine (40 mg, 0.1 mmol) in ethanol (0.8 mL) and water (0.2 mL), sodium tetrahydroborate (4.5 mg, 0.12 mmol) was added and the mixture was heated at 90° C. for 15 minutes. Sodium tetrahydroborate (4.5 mg, 0.12 mmol) was added and the mixture was heated to 90° C. for 15 minutes again. The mixture was evaporated and extracted with ethyl acetate. The organic extracts were evaporated. Purification by preparative LCMS (pH 10) gave the desired compound 11 mg, 30%. 1H NMR (300 MHz, DMSO-d6) δ 8.62 (s, 1H), 8.50 (m, 1H), 7.80 (m, 1H), 7.40 (m, 1H), 6.35 (m, 1H), 5.61 (s, 1H), 4.78 (s, 2H), 4.60 (m, 1H), 4.20 (m, 1H), 3.98 (m, 1H), 2.20 (s, 3H), 2.01 (s, 3H). LCMS calculated for C18H18FN4O2 (M+H)+: m/z=341.1. found: 340.9.

Workup

temperaturethe mixture was heated to 90° C. for 15 minutes again
customThe mixture was evaporated
extractionextracted with ethyl acetate
customThe organic extracts were evaporated
customPurification by preparative LCMS (pH 10)

Sources & evidence

ORD record: ord-c099cb4d6f8b4fffa1f2549292e42e80
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290514B2

Reaction notes

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