Sodium Cyanide → HCID 118208472, compound

HRID 595303Notes

Reaction equation

HRID 595303 reaction equation
[C-:1]#[N:2].[Na+].[CH3:4][C:5]1[CH:10]=[C:9]([C:11]2[CH:12]=[N:13][N:14]([CH2:16][C:17]3([CH3:20])[CH2:19][O:18]3)[CH:15]=2)[N:8]=[C:7]([NH:21][C:22]2[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][N:23]=2)[CH:6]=1>C(O)C.O>[OH:18][C:17]([CH3:20])([CH2:16][N:14]1[CH:15]=[C:11]([C:9]2[CH:10]=[C:5]([CH3:4])[CH:6]=[C:7]([NH:21][C:22]3[CH:27]=[C:26]([C:28]([F:29])([F:30])[F:31])[CH:25]=[CH:24][N:23]=3)[N:8]=2)[CH:12]=[N:13]1)[CH2:19][C:1]#[N:2]

Participants

5

Reactant 2

HCID 8929Sodium CyanideHCID 118208669HCID 118208669, compound

Product 1

HCID 118208472HCID 118208472, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Sodium cyanide (113 mg, 2.3 mmol) was added to 4-methyl-6-(1-((2-methyloxiran-2-yl)methyl)-1H-pyrazol-4-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)pyridin-2-amine (180 mg, 0.46 mmol) in ethanol (5 mL) and water (3 mL), and the mixture was stirred at room temperature for 18 h. The mixture was passed through CELITE, washed with methanol, and concentrated under reduced pressure. The resultant residue was purified by column chromatography on silica gel (0-20% EtOAc/Hexane) to afford 3-hydroxy-3-methyl-4-(4-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)-1H-pyrazol-1-yl)butanenitrile. The racemic mixture was purified by chiral SFC (Chiralpak column, MeOH+0.25% DMEA) to afford (S or R)-3-hydroxy-3-methyl-4-(4-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)-1H-pyrazol-1-yl)butanenitrile (Isomer 1, first eluting): MS ESI calc'd. for C20H20F3N6O [M+H]+ 417. found 417. 1H NMR (500 MHz, DMSO-d6) δ 10.07 (s, 1H), 8.61 (s, 1H), 8.46 (d, J=5 Hz, 1H), 8.15 (s, 1H), 7.96 (s, 1H), 7.17 (d, J=5 Hz, 1H), 7.11 (s, 1H), 7.02 (s, 1H), 5.55 (s, 1H), 4.15 (s, 2H), 2.71-2.64 (m, 2H), 2.28 (s, 3H), 1.18 (s, 3H).

Workup

  1. washwashed with methanol
  2. concentrationconcentrated under reduced pressure
  3. customThe resultant residue was purified by column chromatography on silica gel (0-20% EtOAc/Hexane)

Sources & evidence

ORD record
ord-14dce9f4473145efa2d3cdfacc5db5e2
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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