Methanol → 2-(Trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-7-ol

HRID 1691425Notes

Reaction equation

[OH:1][C:2]1[C:7]2[NH:8][C:9](=O)[C:10]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[N:13][C:11]=3[NH:12][C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH3:22][OH:23]>C1COCC1>[F:20][C:17]([F:18])([F:19])[C:14]1[CH:15]=[CH:16][C:10]2[CH2:9][NH:8][C:7]3=[C:2]([OH:1])[CH:3]=[CH:4][CH:5]=[C:6]3[NH:12][C:11]=2[N:13]=1.[F:20][C:17]([F:18])([F:19])[C:14]1[CH:15]=[CH:16][C:10]2[CH2:9][NH:8][C:7]3[CH:2]=[CH:3][CH:4]=[C:22]([OH:23])[C:6]=3[NH:12][C:11]=2[N:13]=1

Participants

Conditions

Temperature: 40 °C

Procedure

To 7-hydroxy-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-5-one (113 g, 0.38 mol) in THF (1.7 L) at 0° C. was added BH3 (1 M/THF, 1.5 L, 1.5 mol). After gas evolution subsided, the reaction was heated at 40° C. for 1 h. The reaction mixture was cooled to 0° C. and poured slowly into methanol. The resulting solution was partially concentrated, diluted with ethyl acetate, washed with 1 N HCl, saturated NaHCO3 and brine, dried over MgSO4, filtered and concentrated. The residue was slurried in heptane, and the solid was collected by filtration to give the title compound as a 1:1 mixture with 2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-10-ol.

Workup

temperatureThe reaction mixture was cooled to 0° C.
concentrationThe resulting solution was partially concentrated
additiondiluted with ethyl acetate
washwashed with 1 N HCl, saturated NaHCO3 and brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
filtrationthe solid was collected by filtration

Sources & evidence

ORD record: ord-82380e69cb77491babb2cb46e39821ed
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08153626B2

Reaction notes

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