5-Fluoro-2-(trifluoromethyl)pyridine-4-carboxylic acid → {1-{1-[5-Fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile

HRID 1617379Notes

Reaction equation

HRID 1617379 reaction equation
Cl.Cl.Cl.[NH:4]1[CH2:9][CH2:8][CH:7]([N:10]2[CH2:13][C:12]([CH2:36][C:37]#[N:38])([N:14]3[CH:18]=[C:17]([C:19]4[C:20]5[CH:27]=[CH:26][N:25](COCC[Si](C)(C)C)[C:21]=5[N:22]=[CH:23][N:24]=4)[CH:16]=[N:15]3)[CH2:11]2)[CH2:6][CH2:5]1.[F:39][C:40]1[C:45]([C:46](O)=[O:47])=[CH:44][C:43]([C:49]([F:52])([F:51])[F:50])=[N:42][CH:41]=1>>[F:39][C:40]1[C:45]([C:46]([N:4]2[CH2:9][CH2:8][CH:7]([N:10]3[CH2:13][C:12]([CH2:36][C:37]#[N:38])([N:14]4[CH:18]=[C:17]([C:19]5[C:20]6[CH:27]=[CH:26][NH:25][C:21]=6[N:22]=[CH:23][N:24]=5)[CH:16]=[N:15]4)[CH2:11]3)[CH2:6][CH2:5]2)=[O:47])=[CH:44][C:43]([C:49]([F:51])([F:50])[F:52])=[N:42][CH:41]=1

Participants

3

Reactant 2

HCID 673909945-Fluoro-2-(trifluoromethyl)pyridine-4-carboxylic acidHCID 67391102{1-piperidin-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 trihydrochloride

Product 1

HCID 58431311{1-{1-[5-Fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile

Procedure

Reaction of {1-piperidin-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 trihydrochloride with 5-fluoro-2-trifluoromethylisonicotinoic acid following the procedure described for Example 1, followed by HPLC purification (method B) provided the title compound. LC-MS: 554.2 (M+H)+. 1H NMR (400 MHz, DMSO-d6): δ 12.08 (brs, 1H), 8.84 (s, 1H), 8.76 (s, 1H), 8.63 (s, 1H), 8.36 (s, 1H), 8.09 (d, J=4.80 Hz, 1H), 7.55 (d, J=3.60 Hz, 1H), 7.00 (d, J=3.60 Hz, 1H), 4.02 (m, 1H), 3.69 (m, 2H), 3.52 (m, 2H), 3.49 (s, 2H), 3.34 (m, 1H), 3.20 (m, 1H), 3.00 (m, 1H), 2.49 (m, 1H), 1.70 (m, 1H), 1.57 (m, 1H), 1.22 (m, 2H).

Workup

  1. customfollowed by HPLC purification (method B)

Sources & evidence

ORD record
ord-9e127a3e5d83411aad69fc9f6b231a12
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

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