Trifluoroacetic acid → HCID 58180875, compound

HRID 1772843Notes

Reaction equation

HRID 1772843 reaction equation
[C:1]([CH2:3][CH:4]([N:26]1[CH:30]=[C:29]([C:31]2[C:32]3[CH:39]=[CH:38][N:37](COCC[Si](C)(C)C)[C:33]=3[N:34]=[CH:35][N:36]=2)[CH:28]=[N:27]1)[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][C:15]=2[F:22])=[O:13])[CH2:8][CH:7]1[CH:23]([F:25])[F:24])#[N:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([CH2:3][CH:4]([N:26]1[CH:30]=[C:29]([C:31]2[C:32]3[CH:39]=[CH:38][NH:37][C:33]=3[N:34]=[CH:35][N:36]=2)[CH:28]=[N:27]1)[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][C:15]=2[F:22])=[O:13])[CH2:8][CH:7]1[CH:23]([F:24])[F:25])#[N:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67055048HCID 67055048, compound

Product 1

HCID 58180875HCID 58180875, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-{[4-{3-cyano-2-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}-3-(difluoromethyl)piperazin-1-yl]carbonyl}-3-fluorobenzonitrile (27 mg, 0.041 mmol; Peak 3 from Step 8) was stirred in a 1:1 mixture of TFA:DCM (4 mL) for 1 h. Solvent was removed in vacuo. The residue was dissolved in methanol (1.9 mL), and 0.2 mL of ammonium hydroxide aqueous solution was added. Preparative HPLC-MS (C18, eluting with a gradient of H2O/MeCN containing 0.15% NH4OH) afforded purified product (7.7 mg, 35%). 1H NMR (400 MHz, DMSO-d6, rotamers): δ 12.13 (br s, 1H), 8.82 (s, 0.55H), 8.81 (s, 0.45H), 8.68 (s, 0.45H), 8.68 (s, 0.55H), 8.38 (s, 0.45H), 8.37 (s, 0.55H), 8.01 (dd, 0.45H), 7.96 (dd, 0.55H), 7.81 (dd, 0.45H), 7.76 (br d, 0.55H), 7.65-7.57 (m, 2H), 6.97 (d, 1H), 6.24 (br t, 1H), 4.91 (ddd, 1H), 4.25 (d, 0.55H), 4.05 (br m, 0.45H), 3.53-2.33 (m, 10H); 19F NMR (400 MHz, DMSO-d6): −114.10 to −115.21 (m, 1F), −123.22 to −125.01 (m, 2F); LCMS (M+H)+: 534.2.

Workup

  1. customSolvent was removed in vacuo
  2. dissolutionThe residue was dissolved in methanol (1.9 mL)
  3. addition0.2 mL of ammonium hydroxide aqueous solution was added
  4. washPreparative HPLC-MS (C18, eluting with a gradient of H2O/MeCN containing 0.15% NH4OH)
  5. customafforded
  6. custompurified product (7.7 mg, 35%)

Sources & evidence

ORD record
ord-97e0af93015341dba7b39b2d99767ce6
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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