Trifluoroacetic acid → {1-{1-[(1-methyl-1H-pyrazol-5-yl)sulfonyl]piperidin-4-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile

HRID 1617360Notes

Reaction equation

HRID 1617360 reaction equation
[CH3:1][N:2]1[C:6]([S:7]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]3[CH2:19][C:18]([CH2:42][C:43]#[N:44])([N:20]4[CH:24]=[C:23]([C:25]5[C:26]6[CH:33]=[CH:32][N:31](COCC[Si](C)(C)C)[C:27]=6[N:28]=[CH:29][N:30]=5)[CH:22]=[N:21]4)[CH2:17]3)[CH2:12][CH2:11]2)(=[O:9])=[O:8])=[CH:5][CH:4]=[N:3]1.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:1][N:2]1[C:6]([S:7]([N:10]2[CH2:11][CH2:12][CH:13]([N:16]3[CH2:19][C:18]([CH2:42][C:43]#[N:44])([N:20]4[CH:24]=[C:23]([C:25]5[C:26]6[CH:33]=[CH:32][NH:31][C:27]=6[N:28]=[CH:29][N:30]=5)[CH:22]=[N:21]4)[CH2:17]3)[CH2:14][CH2:15]2)(=[O:9])=[O:8])=[CH:5][CH:4]=[N:3]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58431363HCID 58431363, compound

Product 1

HCID 58431382{1-{1-[(1-methyl-1H-pyrazol-5-yl)sulfonyl]piperidin-4-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrileYield 64.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of {1-{1-[(1-methyl-1H-pyrazol-5-yl)sulfonyl]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 (56 mg, 0.1 mmol) in methylene chloride (1.5 mL) was added trifluoroacetic acid (1.5 mL). The mixture was stirred at room temperature for 2 hours and concentrated in vacuo. The residue was dissolved in 2 mL of a methanol solution containing 20% ethylenediamine. After being stirred at room temperature for 1 hour, the mixture was purified by HPLC (method B) to give 20 mg (64.5%) of {1-{1-[(1-methyl-1H-pyrazol-5-yl)sulfonyl]piperidin-4-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile. LC-MS: 507.2 (M+H)+. 1H NMR (300 MHz, DMSO-d6): δ 12.08 (brs, 1H), 8.72 (d, 1H), 8.62 (s, 1H), 8.34 (s, 1H), 7.55 (d, 2H), 6.99 (d, 1H), 6.75 (s, 1H), 3.95 (s, 3H), 3.62 (dd, 2H), 3.45 (dd, 2H), 3.40 (m, 2H), 3.25 (s, 2H), 3.19 (m, 1H), 2.75 (m, 2H), 1.70 (m, 2H), 1.25 (m, 2H).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in 2 mL of a methanol solution
  3. additioncontaining 20% ethylenediamine
  4. stirringAfter being stirred at room temperature for 1 hour
  5. customthe mixture was purified by HPLC (method B)

Sources & evidence

ORD record
ord-5018a1579d6b42ff9369b93d6ef24624
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

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