Trifluoroacetic acid → 3-[(4-{3-(Cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}piperidin-1-yl)methyl]-6-(dimethylamino)-2-fluorobenzonitrile

HRID 1617358Notes

Reaction equation

HRID 1617358 reaction equation
[C:1]([CH2:3][C:4]1([N:27]2[CH:31]=[C:30]([C:32]3[C:33]4[CH:40]=[CH:39][N:38](COCC[Si](C)(C)C)[C:34]=4[N:35]=[CH:36][N:37]=3)[CH:29]=[N:28]2)[CH2:7][N:6]([CH:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[C:16]([F:26])=[C:17]([C:20]([N:23]([CH3:25])[CH3:24])=[CH:21][CH:22]=3)[C:18]#[N:19])[CH2:10][CH2:9]2)[CH2:5]1)#[N:2].FC(F)(F)C(O)=O>C(Cl)Cl>[C:1]([CH2:3][C:4]1([N:27]2[CH:31]=[C:30]([C:32]3[C:33]4[CH:40]=[CH:39][NH:38][C:34]=4[N:35]=[CH:36][N:37]=3)[CH:29]=[N:28]2)[CH2:7][N:6]([CH:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[C:16]([F:26])=[C:17]([C:20]([N:23]([CH3:25])[CH3:24])=[CH:21][CH:22]=3)[C:18]#[N:19])[CH2:10][CH2:9]2)[CH2:5]1)#[N:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 584313743-[(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}piperidin-1-yl)methyl]-6-(dimethylamino)-2-fluorobenzonitrile

Product 1

HCID 584313283-[(4-{3-(Cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}piperidin-1-yl)methyl]-6-(dimethylamino)-2-fluorobenzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a reaction vial were added 3-[(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}piperidin-1-yl)methyl]-6-(dimethylamino)-2-fluorobenzonitrile (56 mg, 0.1 mmol), trifluoroacetic acid (1.5 mL) and methylene chloride (1.5 mL). The mixture was stirred at room temperature for 1 hour and concentrated in vacuum. The residue was dissolved in 5 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 the title compound. LC-MS: 539.2 (M+H)+. 1H NMR (400 MHz, DMSO-d6): δ 12.10 (s, 1H), 8.79 (s, 1H), 8.67 (s, 1H), 8.39 (s, 1H), 7.59 (d, J=3.6 Hz, 1H), 7.42 (t, J=8.8 Hz, 1H), 7.05 (d, J=3.6 Hz, 1H), 6.78 (d, J=8.8 Hz, 1H), 3.68 (d, J=8.4 Hz, 2H), 3.51 (m, 4H), 3.38 (s, 2H), 3.01 (s, 6H), 2.67 (m, 2H), 2.17 (m, 1H), 1.97 (m, 2H), 1.63 (m, 2H), 1.15 (m, 2H).

Workup

  1. concentrationconcentrated in vacuum
  2. dissolutionThe residue was dissolved in 5 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-50fa1896ec2247aebf7e5e69d321b841
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

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