Sodium triacetoxyborohydride → HCID 178458732, compound

HRID 2200821Notes

Reaction equation

HRID 2200821 reaction equation
Cl.Cl.[CH3:3][Si:4]([CH3:31])([CH3:30])[CH2:5][CH2:6][O:7][CH2:8][N:9]1[C:13]2[N:14]=[CH:15][N:16]=[C:17]([C:18]3[CH:19]=[N:20][N:21]([C:23]4([CH2:27][C:28]#[N:29])[CH2:26][NH:25][CH2:24]4)[CH:22]=3)[C:12]=2[CH:11]=[CH:10]1.[OH:32][C:33]([C:36]1[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[N:39]=[C:38]([O:46][CH:47]2[CH2:52][CH2:51][C:50](=O)[CH2:49][CH2:48]2)[CH:37]=1)([CH3:35])[CH3:34].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[OH:32][C:33]([C:36]1[CH:41]=[C:40]([C:42]([F:43])([F:44])[F:45])[N:39]=[C:38]([O:46][C@@H:47]2[CH2:52][CH2:51][C@H:50]([N:25]3[CH2:24][C:23]([CH2:27][C:28]#[N:29])([N:21]4[CH:22]=[C:18]([C:17]5[C:12]6[CH:11]=[CH:10][N:9]([CH2:8][O:7][CH2:6][CH2:5][Si:4]([CH3:30])([CH3:3])[CH3:31])[C:13]=6[N:14]=[CH:15][N:16]=5)[CH:19]=[N:20]4)[CH2:26]3)[CH2:49][CH2:48]2)[CH:37]=1)([CH3:34])[CH3:35]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 67391464{3-[4-(7-{[2-(Trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile dihydrochlorideHCID 712577644-{[4-(1-Hydroxy-1-methylethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexanone

Product 1

HCID 178458732HCID 178458732, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

{3-[4-(7-{[2-(Trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile dihydrochloride (55.3 mg, 0.115 mmol) and 4-{[4-(1-hydroxy-1-methylethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexanone were dissolved in dry 1,2-dichloroethane (1.38 mL) and were stirred for 5 min and sodium triacetoxyborohydride (86.1 mg, 0.406 mmol) was added. The reaction mixture was stirred at 25° C. for 16 h, at which time LCMS analysis showed mainly the two diastereomeric products. The reaction was quenched with water, neutralized with NaHCO3 and extracted with ethyl acetate and the solvent was evaporated. The residue was purified by LCMS (pH 10) and the fractions containing the second peak were combined and evaporated to give {1-(cis-4-{[4-(1-hydroxy-1-methylethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile. The first peak was also isolated to give {1-(trans-4-{[4-(1-hydroxy-1-methyl ethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile. MS (ES): 712(M+1).

Workup

  1. stirringThe reaction mixture was stirred at 25° C. for 16 h, at which time LCMS analysis
  2. customThe reaction was quenched with water
  3. extractionextracted with ethyl acetate
  4. customthe solvent was evaporated
  5. customThe residue was purified by LCMS (pH 10)
  6. additionthe fractions containing the second peak
  7. customevaporated

Sources & evidence

ORD record
ord-684140050e164519902564b8a04f0591
Source dataset
uspto-grants-2016_06
Patent number
US09359358B2

Reaction notes

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