Trifluoroacetic acid → 3-(hydroxymethyl)-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutylacetonitrile

HRID 1692916Notes

Reaction equation

HRID 1692916 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:6][C:5]([CH2:29][C:30]#[N:31])([N:7]2[CH:11]=[C:10]([C:12]3[C:13]4[CH:20]=[CH:19][N:18](COCC[Si](C)(C)C)[C:14]=4[N:15]=[CH:16][N:17]=3)[CH:9]=[N:8]2)[CH2:4]1.C(O)(C(F)(F)F)=O>>[OH:1][CH2:2][CH:3]1[CH2:4][C:5]([CH2:29][C:30]#[N:31])([N:7]2[CH:11]=[C:10]([C:12]3[C:13]4[CH:20]=[CH:19][NH:18][C:14]=4[N:15]=[CH:16][N:17]=3)[CH:9]=[N:8]2)[CH2:6]1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 670172063-(hydroxymethyl)-1-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutylacetonitrile

Product 1

HCID 442319743-(hydroxymethyl)-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutylacetonitrile

Procedure

To 3-(hydroxymethyl)-1-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutylacetonitrile (0.030 g, 0.000068 mol) was added 1.5 mL of TFA. The reaction was stirred at rt for 30 min, then evaporated to dryness. The crude mixture was dissolved in 1 mL of methanol and treated with 60 μL of ethylenediamine at rt for 5 h. The resulting mixture was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.15% NH4OH) to give the desired products as free bases. First peak retention time 0.766 min, LCMS calculated for C1-6H71N6O(M+H)+: 309.1; Found: 309.3. 1H NMR (400 MHz, DMSO-d6): δ 12.11(1H, br s), 8.67 (1H, s), 8.65 (1H, s), 8.37 (1H, s), 7.58 (1H, d, J=3.6), 7.02 (1H, d, J=3.6 Hz), 4.69 (1H, br s), 3.47 (2H, s), 3.41 (2H, br s), 2.53 (2H, m), 2.37 (2H, m) ppm. Second peak retention time 0.805 min, LCMS calculated for C16H17N6O(M+H)+: 309. 1; Found: 309.3. 1H NMR (400 MHz, DMSO-d6): δ 12.11(1H, br s), 8.80 (1H, s), 8.68 (1H, s), 8.40 (1H, s), 7.58 (1H, d, J=3.6 Hz), 7.07 (1H, d J=3.6 Hz), 4.78 (1H, br t, J=5.2 Hz), 3.47 (2H, br t, J=5.2 Hz), 3.36 (2H, s), 2.85 (2H, m), 2.29 (2H, m), ppm.

Workup

  1. customevaporated to dryness
  2. dissolutionThe crude mixture was dissolved in 1 mL of methanol
  3. additiontreated with 60 μL of ethylenediamine at rt for 5 h
  4. customThe resulting mixture was purified on RP-HPLC (XBridge C18 column
  5. washeluting with a gradient of acetonitrile/water containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-03d5afc812b1460f9b89b92da12a7724
Source dataset
uspto-grants-2012_04
Patent number
US08158616B2

Reaction notes

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