Triethylamine → 2-[1-[(3R,4S)-3-fluoro-1-[3-fluoro-2-(trifluoromethyl)pyridine-4-carbonyl]piperidin-4-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]azetidin-3-yl]acetonitrile

HRID 1617389Notes

Reaction equation

HRID 1617389 reaction equation
[F:1][C@H:2]1[C@@H:7]([N:8]2[CH2:11][C:10]([CH2:34][C:35]#[N:36])([N:12]3[CH:16]=[C:15]([C:17]4[C:18]5[CH:25]=[CH:24][N:23](COCC[Si](C)(C)C)[C:19]=5[N:20]=[CH:21][N:22]=4)[CH:14]=[N:13]3)[CH2:9]2)[CH2:6][CH2:5][NH:4][CH2:3]1.[F:37][C:38]1[C:46]([C:47]([F:50])([F:49])[F:48])=[N:45][CH:44]=[CH:43][C:39]=1[C:40](O)=[O:41].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C>[F:1][C@H:2]1[C@@H:7]([N:8]2[CH2:9][C:10]([CH2:34][C:35]#[N:36])([N:12]3[CH:16]=[C:15]([C:17]4[C:18]5[CH:25]=[CH:24][NH:23][C:19]=5[N:20]=[CH:21][N:22]=4)[CH:14]=[N:13]3)[CH2:11]2)[CH2:6][CH2:5][N:4]([C:40](=[O:41])[C:39]2[CH:43]=[CH:44][N:45]=[C:46]([C:47]([F:50])([F:48])[F:49])[C:38]=2[F:37])[CH2:3]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 265964893-Fluoro-2-(trifluoromethyl)isonicotinic acidHCID 67390728{1-[cis-3-Fluoropiperidin-4-yl]-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile

Product 1

HCID 673915632-[1-[(3R,4S)-3-fluoro-1-[3-fluoro-2-(trifluoromethyl)pyridine-4-carbonyl]piperidin-4-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]azetidin-3-yl]acetonitrileYield 21.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a 20 mL vial were added {1-[cis-3-fluoropiperidin-4-yl]-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile (200 mg, 0.4 mmol) in DMF (3 mL), 3-fluoro-2-(trifluoromethyl)isonicotinic acid (99 mg, 0.47 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (225 mg, 0.509 mmol) and triethylamine (0.14 mL, 1.0 mmol). The mixture was stirred at room temperature overnight and purified with prep-LCMS to give 50 mg of the desired compound as a white solid. LC/MS found: 702.2 (M+1)+.

Workup

  1. custompurified with prep-LCMS

Sources & evidence

ORD record
ord-8de9c53841904eb6b2ea9bec49bc89c5
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

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