Trifluoroacetic acid → 4-{1-[1-methyl-2-(4-{[5-methyl-2-(trifluoromethyl)-3-furyl]sulfonyl}piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}-7H-pyrrolo[2,3-d]pyrimidine

HRID 1772811Notes

Reaction equation

HRID 1772811 reaction equation
[CH3:1][CH:2]([N:10]1[CH:14]=[C:13]([C:15]2[C:16]3[CH:23]=[CH:22][N:21](COCC[Si](C)(C)C)[C:17]=3[N:18]=[CH:19][N:20]=2)[CH:12]=[N:11]1)[CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.C(N(CC)CC)C.[CH3:39][C:40]1[O:44][C:43]([C:45]([F:48])([F:47])[F:46])=[C:42]([S:49](Cl)(=[O:51])=[O:50])[CH:41]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:1][CH:2]([N:10]1[CH:14]=[C:13]([C:15]2[C:16]3[CH:23]=[CH:22][NH:21][C:17]=3[N:18]=[CH:19][N:20]=2)[CH:12]=[N:11]1)[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([S:49]([C:42]2[CH:41]=[C:40]([CH3:39])[O:44][C:43]=2[C:45]([F:48])([F:46])[F:47])(=[O:51])=[O:50])[CH2:6][CH2:5]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 27798955-methyl-2-(trifluoromethyl)furan-3-sulfonyl ChlorideHCID 670549204-[1-(1-methyl-2-piperazin-1-ylethyl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 670549594-{1-[1-methyl-2-(4-{[5-methyl-2-(trifluoromethyl)-3-furyl]sulfonyl}piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}-7H-pyrrolo[2,3-d]pyrimidineYield 41.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-[1-(1-methyl-2-piperazin-1-ylethyl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (16.0 mg, 0.036 mmol) in DCM (0.3 mL) was added triethylamine (7.6 μL, 0.054 mmol) followed by 5-methyl-2-(trifluoromethyl)furan-3-sulfonyl chloride (11 mg, 0.043 mmol). The reaction was stirred at room temperature for 1 h and trifluoroacetic acid (0.5 mL) was added to reaction vial. After stirring for 1 hour, the solvent was removed in vacuo. The residue was dissolved in methanol (1 mL) and treated with ethylenediamine (0.1 mL). The reaction solution was stirred for 1 hour and diluted with methanol and purified with preparative LCMS (C18 column eluting with a gradient of MeCN/H2O containing 0.15% NH4OH) to give the desired product as white solid (7.8 mg, 41%). 1H NMR (300 MHz, DMSO-D6): δ 12.17 (s, 1H); 8.73 (s, 2H); 8.34 (s, 1H); 7.64 (d, 1H); 7.59 (d, 1H); 7.03 (d, 1H); 4.76 (m, 1H); 3.02 (m, 5H); 2.78-2.50 (m, 5H); 1.53 (d, 3H); LCMS calculated for C22H25F3N7O3S(M+H)+: m/z=524.1.

Workup

  1. stirringAfter stirring for 1 hour
  2. customthe solvent was removed in vacuo
  3. dissolutionThe residue was dissolved in methanol (1 mL)
  4. additiontreated with ethylenediamine (0.1 mL)
  5. stirringThe reaction solution was stirred for 1 hour
  6. additiondiluted with methanol
  7. custompurified with preparative LCMS (C18 column
  8. washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-9d0ceca59891461e904a8b92d6ace32a
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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