Dichloromethane → HCID 58181009, compound

HRID 1772836Notes

Reaction equation

HRID 1772836 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[CH2:23][O:24][CH3:25])#[N:2].C(Cl)Cl>C(O)(C(F)(F)F)=O>[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[CH2:23][O:24][CH3:25])#[N:2]

Participants

4

Reactant 2

HCID 6344DichloromethaneHCID 67055040HCID 67055040, compound

Product 1

HCID 58181009HCID 58181009, compoundYield 68.5%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

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-(methoxymethyl)piperazin-1-yl]carbonyl}-3-fluorobenzonitrile (12 mg, 0.018 mmol; Peak 2 from Step 5) was dissolved in a 1:1 mixture of TFA:DCM (3 mL) and was stirred for 1 h. Solvent was removed in vacuo. The residue was then stirred in a solution of methanol (1.5 mL), containing ammonium hydroxide solution (0.15 mL). Purification via preparative HPLC-MS (C18 eluting with a gradient of H2O/MeCN containing 0.15% NH4OH) afforded product (6.5 mg, 67%). 1H NMR (400 MHz, DMSO-d6): δ 12.12 (br s, 1H), 8.81 (s, 0.6H), 8.79 (s, 0.4H), 8.68 (s, 0.6H), 8.67 (s, 0.4H), 8.37 (s, 1H), 8.00-7.94 (m, 1H), 7.80-7.73 (m, 1H), 7.63-7.55 (m, 2H), 6.98 (d, 0.6H), 6.97 (d, 0.4H), 4.90-4.76 (tt, 1H), 3.71-2.12 (m, 16H); 19F NMR (400 MHz, DMSO-d6): δ −114.74 (s, 1F), LCMS (M+H)+: 528.0.

Workup

  1. customSolvent was removed in vacuo
  2. additioncontaining ammonium hydroxide solution (0.15 mL)
  3. customPurification via preparative HPLC-MS (C18
  4. washeluting with a gradient of H2O/MeCN containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-c6adb5a8d83b4c3ab354634b14e342a4
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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