Ethylenediamine → Trifluoroacetic acid
Reaction equation
[CH2:1]([S:3]([N:6]1[CH2:9][C:8]([N:12]2[CH:16]=[C:15]([C:17]3[C:18]4[CH:25]=[CH:24][N:23](COCC[Si](C)(C)C)[C:19]=4[N:20]=[CH:21][N:22]=3)[CH:14]=[N:13]2)([CH2:10][F:11])[CH2:7]1)(=[O:5])=[O:4])[CH3:2].[C:34]([OH:40])([C:36]([F:39])([F:38])[F:37])=[O:35].C(N)CN>>[CH2:1]([S:3]([N:6]1[CH2:7][C:8]([N:12]2[CH:16]=[C:15]([C:17]3[C:18]4[CH:25]=[CH:24][NH:23][C:19]=4[N:20]=[CH:21][N:22]=3)[CH:14]=[N:13]2)([CH2:10][F:11])[CH2:9]1)(=[O:4])=[O:5])[CH3:2].[C:34]([OH:40])([C:36]([F:39])([F:38])[F:37])=[O:35]Participants
Reactant 3
Product 2
Procedure
4-{1-[1-(Ethylsulfonyl)-3-(fluoromethyl)azetidin-3-yl]-1H-pyrazol-4-yl}-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (0.060 g, 0.12 mmol) was treated with 2 mL of TFA at rt for 30 min. The reaction mixture was evaporated to dryness. LCMS (M+H) 395.3. The resulting residue was dissolved in 3 mL of methanol and treated with ethylenediamine (0.0811 mL, 1.21 mmol) at rt for 30 min. The mixture was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetone/water containing 0.2% TFA) to give the desired product as TFA salt. LCMS calculated for C15H18FN6O2S(M+H)+ (free base): m/z=365.1; Found: 365.3. 1H NMR (DMSO-d6, 300 MHz) δ 12.57 (1H, br s), 8.94 (1H, s), 8.81 (1H, s), 8.53 (1H, s), 7.75 (1H, br s), 7.21 (1H, br s), 5.03 (2H, d, J=46.8 Hz), 4.53 (1H, dd, J=9.0 and 2.7 Hz), 4.24 (1H, d, J=9.0 Hz), 3.25 (2H, q, J=7.2 Hz), 1.23 (3H, t, J=7.2 Hz) ppm. 19F NMR (DMSO-d6, 300 MHz) δ −74.98 (3F, s), −225.56 (1F, t, J=48.3 Hz) ppm.
Workup
- customThe reaction mixture was evaporated to dryness
- dissolutionThe resulting residue was dissolved in 3 mL of methanol
- customThe mixture was purified on RP-HPLC (XBridge C18 column
- washeluting with a gradient of acetone/water containing 0.2% TFA)
Sources & evidence
- ORD record
- ord-c174c8c89c4742db84079400f19de97a
- Source dataset
- uspto-grants-2012_04
- Patent number
- US08158616B2
Reaction notes
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