Water → 4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-2,5-difluoro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide

HRID 2363326Notes

Reaction equation

HRID 2363326 reaction equation
B(F)(F)F.CCOCC.[C:10]([CH2:12][C:13]1([N:34]2[CH:38]=[C:37]([C:39]3[C:40]4[CH:47]=[CH:46][N:45](COCC[Si](C)(C)C)[C:41]=4[N:42]=[CH:43][N:44]=3)[CH:36]=[N:35]2)[CH2:16][N:15]([C:17]2[C:31]([F:32])=[CH:30][C:20]([C:21]([NH:23][C@@H:24]([CH3:29])[C:25]([F:28])([F:27])[F:26])=[O:22])=[C:19]([F:33])[CH:18]=2)[CH2:14]1)#[N:11].O.[OH-].[NH4+]>C(#N)C>[C:10]([CH2:12][C:13]1([N:34]2[CH:38]=[C:37]([C:39]3[C:40]4[CH:47]=[CH:46][NH:45][C:41]=4[N:42]=[CH:43][N:44]=3)[CH:36]=[N:35]2)[CH2:16][N:15]([C:17]2[C:31]([F:32])=[CH:30][C:20]([C:21]([NH:23][C@@H:24]([CH3:29])[C:25]([F:27])([F:28])[F:26])=[O:22])=[C:19]([F:33])[CH:18]=2)[CH2:14]1)#[N:11]

Participants

6

Reactant 4

HCID 962Water2×HCID 8000Boron trifluoride etherateHCID 14923Ammonium HydroxideHCID 712084164-{3-(cyanomethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-2,5-difluoro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide

Product 1

HCID 711553744-{3-(cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-2,5-difluoro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Boron trifluoride etherate (0.051 mL, 0.40 mmol) was added to a solution of 4-{3-(cyanomethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-2,5-difluoro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide in acetonitrile (1.0 mL) at 0° C. under N2. The reaction mixture was stirred at room temperature for 3 h. (LCMS (M+H)+: m/z=561.3). Then the mixture was cooled to 0° C., water (0.13 mL) was added. After 30 min, 5.0 M ammonium hydroxide in water (0.2 mL, 1 mmol) was added slowly at 0° C. over 5 min. The reaction mixture was stirred at room temperature overnight, and purified by RP-HPLC (pH=10) to afford the desired product. LCMS (M+H)+: m/z=531.0. 1H NMR (400 MHz, DMSO-d6): δ 12.62 (br, 1H), 9.07 (s, 1H), 8.84 (s, 1H), 8.55 (s, 1H), 8.51 (dd, J=8.8, 1.2 Hz, 1H), 7.78 (br, 1H), 7.35 (dd, J=12.6, 6.5 Hz, 1H), 7.23 (d, J=1.9 Hz, 1H), 6.65 (dd, J=11.9, 7.3 Hz, 1H), 4.76 (m, 1H), 4.70 (d, J=9.3 Hz, 2H), 4.44 (d, J=9.2 Hz, 2H), 3.76 (s, 2H), 1.30 (d, J=7.1 Hz, 3H).

Workup

  1. temperatureThen the mixture was cooled to 0° C.
  2. waitAfter 30 min
  3. stirringThe reaction mixture was stirred at room temperature overnight
  4. custompurified by RP-HPLC (pH=10)

Sources & evidence

ORD record
ord-a7f70e183cd64244a4a74e167b990ba8
Source dataset
uspto-grants-2014_04
Patent number
US08691807B2

Reaction notes

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