Methanol → HCID 118161685, compound

HRID 2203673Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([CH:13]3[CH:24]4[CH:14]3[CH2:15][CH:16]3[N:21]([CH3:22])[C:20](=O)[CH2:19][O:18][CH:17]34)[N:10]([CH:25]([CH3:27])[CH3:26])[N:9]=2)=[CH:4][C:3]=1[C:28]([F:31])([F:30])[F:29].CO>O1CCCC1>[CH:25]([N:10]1[C:11]([CH:13]2[CH:24]3[CH:14]2[CH2:15][CH:16]2[N:21]([CH3:22])[CH2:20][CH2:19][O:18][CH:17]23)=[CH:12][C:8]([C:5]2[CH:4]=[C:3]([C:28]([F:30])([F:31])[F:29])[C:2]([NH2:1])=[N:7][CH:6]=2)=[N:9]1)([CH3:27])[CH3:26]

Participants

Conditions

Temperature: 70 °C

Procedure

To a stirred solution of (±)-6-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-4-methylhexahydro-2H-cyclopropa[4,5]cyclopenta[1,2-b][1,4]oxazin-3(6bH)-one (0.040 g, 0.092 mmol) in tetrahydrofuran (5 mL) was added borane tetrahydrofuran complex (5 mL, 5 mmol). The reaction mixture was heated at 70° C. for 2 h under nitrogen. Methanol was added and the resulting solution was concentrated in vacuo. Purification by preparative HPLC afforded a 1.5:1 mixture of diastereomers (15 mg, 39%). LCMS (ESI): [MH]+=401.9 1H NMR (400 MHz, Methanol-d4) δ: 8.52 (d, J=3.6 Hz, 1 H), 8.32 (s, 1 H), 8.13 (s, 1 H), 6.31 (s, 0.6 H), 6.22 (s, 0.4 H), 4.85-4.82 (m, 1H), 4.06-4.02 (m, 1 H), 3.85-3.70 (m, 1.6 H), 3.50-3.45 (m, 0.4 H), 3.40-3.30 (m, 0.6 H), 3.20-3.17 (m, 0.4 H), 2.90-2.85 (m, 0.6 H), 2.79-2.65 (m, 3.4 H), 2.60 (s, 1 H), 2.37-2.36 (m, 1 H), 2.05-1.95 (m, 2 H), 1.90-1.80 (m, 1 H), 1.55-1.52 (m, 6 H).

Workup

concentrationthe resulting solution was concentrated in vacuo
customPurification by preparative HPLC
customafforded
additiona 1.5:1 mixture of diastereomers (15 mg, 39%)

Sources & evidence

ORD record: ord-0af83312d8a740e19dd4195b0ebc9705
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365583B2

Reaction notes

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