Sodium borohydride → HCID 67471135, compound

HRID 2202159Notes

Reaction equation

HRID 2202159 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([CH:13]3[CH2:18][CH2:17][N:16]([CH2:19][C:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[O:21])[CH2:15][CH2:14]3)[N:10]([C:28]3[N:33]=[CH:32][CH:31]=[CH:30][N:29]=3)[N:9]=2)=[CH:4][CH:3]=1.[BH4-].[Na+]>CO.CCOC(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]=[C:11]([CH:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[OH:21])[CH2:15][CH2:14]3)[N:10]([C:28]3[N:29]=[CH:30][CH:31]=[CH:32][N:33]=3)[N:9]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 71251917HCID 71251917, compound

Product 1

HCID 67471135HCID 67471135, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the product of EXAMPLE 74 (90.0 mg, 0.20 mmol) in methanol (1.0 ml) was added sodium borohydride (15.4 mg, 0.407 mmol). After stirring at ambient temperature for 1 hour, the reaction mixture was diluted with EtOAc, and washed with water and brine. The organic layer was separated, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified using a silica gel cartridge (a gradient of 0-10% methanol in dichloromethane) to give racemic 2-{4-[3-(4-fluorophenyl)-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl]piperidin-1-yl}-1-phenylethanol as a light yellow solid. LC-MS (m/z): 445.10 [M+H]+. 1H NMR (CDCl3, 500 MHz): δ 8.90 (d, J=4.8 Hz, 2H), 8.23-8.29 (m, 2H), 7.35-7.37 (m, 4H), 7.29-7.34 (m, 1H), 7.13-7.17 (m, 3H), 4.80 (dd, J=10.4 Hz, 3.4 Hz, 1H), 4.28-4.34 (br, 1H), 3.81-3.87 (br. 1H), 3.34 (d, J=11.4 Hz, 1H), 3.01 (d, J=1.4 Hz, 1H), 2.50-2.63 (m, 3H), 2.02-2.29 (m, 4H). The racemic 2-{4-[3-(4-fluorophenyl)-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl]piperidin-1-yl}-1-phenylethanol was resolved using ChiralPak™ AD column using 60% IPA in heptane to give a faster eluting enantiomer and a slower eluting enantiomer.

Workup

  1. washwashed with water and brine
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified

Sources & evidence

ORD record
ord-b4ba55e4deb64387b6eaf15e8f2bffff
Source dataset
uspto-grants-2016_06
Patent number
US09365539B2

Reaction notes

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