1,2-Dichloroethane → HCID 178504215, compound

HRID 2200804Notes

Reaction equation

HRID 2200804 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.O=[C:33]1[CH2:38][CH2:37][CH:36]([O:39][C:40]2[N:45]=[C:44]([C:46]([F:49])([F:48])[F:47])[N:43]=[C:42]([C:50]([OH:52])=[O:51])[CH:41]=2)[CH2:35][CH2:34]1.ClCCCl.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[C:28]([CH2:27][C:23]1([N:21]2[CH:22]=[C:18]([C:17]3[C:12]4[CH:11]=[CH:10][N:9]([CH2:8][O:7][CH2:6][CH2:5][Si:4]([CH3:30])([CH3:3])[CH3:31])[C:13]=4[N:14]=[CH:15][N:16]=3)[CH:19]=[N:20]2)[CH2:24][N:25]([C@@H:33]2[CH2:38][CH2:37][C@H:36]([O:39][C:40]3[N:45]=[C:44]([C:46]([F:48])([F:47])[F:49])[N:43]=[C:42]([C:50]([OH:52])=[O:51])[CH:41]=3)[CH2:35][CH2:34]2)[CH2:26]1)#[N:29]

Participants

5

Reactant 4

HCID 111,2-DichloroethaneHCID 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 71257331HCID 71257331, compound

Product 1

HCID 178504215HCID 178504215, compound

Conditions

Temperature
25 °C

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 (500.0 mg, 1.036 mmol) and 6-[(4-oxocyclohexyl)oxy]-2-(trifluoromethyl)pyrimidine-4-carboxylic acid in dry 1,2-dichloroethane (14.36 mL, 182.3 mmol) were stirred for 5 minutes and sodium triacetoxyborohydride (898 mg, 4.24 mmol) was added. The reaction mixture was stirred at 25° C. for 16 hours, 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. 1H NMR (400 MHz, CD3OD) δ 8.90 (m, 1H), 8.83 (s, 1H), 8.55 (m, 1H), 7.75 (d, 1H), 7.51 (d, 1H), 7.15 (d, 1H), 5.78 (s, 4H), 5.23 (m, 1H), 3.50-3.70 (m, 3H), 1.40-2.40 (m, 8H). 19F NMR (376 MHz, CD3OD) δ −70.52 (s), −77.53 (s). MS (ES): 698(M+1).

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with ethyl acetate
  3. customthe solvent was evaporated
  4. customThe residue was purified by LCMS (pH 10)
  5. additionthe fractions containing the second peak
  6. customevaporated

Sources & evidence

ORD record
ord-52eec6ccae9b4d98a9cfdba3fb17a65c
Source dataset
uspto-grants-2016_06
Patent number
US09359358B2

Reaction notes

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