Triethylamine → HCID 178480636, compound

HRID 2369841Notes

Reaction equation

HRID 2369841 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:15]=[C:14]([C:16]4[NH:20][N:19]=[C:18]([C:21]5[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][CH:22]=5)[CH:17]=4)[NH:13][C:12]=3[CH:28]=2)[CH2:4][CH2:3]1.[N:29]([C:32]1[CH:37]=[CH:36][C:35]([O:38][C:39]([F:42])([F:41])[F:40])=[CH:34][CH:33]=1)=[C:30]=[O:31].C(N(CC)CC)C>CS(C)=O.CC#N>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]3[NH:15][C:14]([C:16]4[CH:17]=[C:18]([C:21]5[CH:27]=[CH:26][C:24]([NH:25][C:30]([NH:29][C:32]6[CH:37]=[CH:36][C:35]([O:38][C:39]([F:40])([F:41])[F:42])=[CH:34][CH:33]=6)=[O:31])=[CH:23][CH:22]=5)[NH:19][N:20]=4)=[N:13][C:12]=3[CH:28]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 92298p-(Trifluoromethoxy)phenyl isocyanateHCID 135991587HCID 135991587, compound

Product 1

HCID 178480636HCID 178480636, compoundYield 50.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-{5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl}aniline (45 mg, 0.12 mmol) in DMSO (2 mL) were added 1-isocyanato-4-trifluoromethoxybenzene (36.6 mg, 0.18 mmol), triethylamine (36.4 mg, 0.36 mmol) in CH3CN (1 mL) at room temperature. The reaction mixture was monitored by LC-MS until reaction was complete (1 h). The resulting mixture was concentrated in vacuo and separated by preparative HPLC (0.1% TFA/CH3CN, 0.05% TFA/water). The corresponding fractions were concentrated and dried. The resulting solid was dissolved in MeOH (1 mL) and was added 4N HCl (0.5 mL). The solution was concentrated and repeated three times to afford product (24%, 34.7 mg) as light yellow solid as the hydrochloride salt: 1H NMR (400 MHz, DMSO-d6): δ 11.07 (s, 1H), 9.68 (d, 2H), 7.79-7.57 (7H, m), 7.38-7.29 (m, 3H), 7.17 (s, 1H), 3.90 (m, 2H), 3.46 (m, 2H), 3.21 (m, 4H), 2.85 (m, 3H) MS (EI) for C29H27F3N8O2: 577.3 (MH+).

Workup

  1. customThe reaction mixture was monitored by LC-MS until reaction
  2. custom(1 h)
  3. concentrationThe resulting mixture was concentrated in vacuo
  4. customseparated by preparative HPLC (0.1% TFA/CH3CN, 0.05% TFA/water)
  5. concentrationThe corresponding fractions were concentrated
  6. customdried
  7. dissolutionThe resulting solid was dissolved in MeOH (1 mL)
  8. additionwas added 4N HCl (0.5 mL)
  9. concentrationThe solution was concentrated

Sources & evidence

ORD record
ord-ce05043d69de454abe680db2c0ccb0d6
Source dataset
uspto-grants-2014_04
Patent number
US08710038B2

Reaction notes

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