2,6-Lutidine → HCID 136295067, compound

HRID 1476880Notes

Reaction equation

HRID 1476880 reaction equation
Cl.[F:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[C:11]([NH:13][C@H:14]1[CH2:18][CH2:17][NH:16][CH2:15]1)=[N:10][C:9]([C:19]1[NH:23][C:22](=[O:24])[NH:21][N:20]=1)=[CH:8]2.CC1C=CC=C(C)N=1.[C:33](Cl)(=[O:36])[CH:34]=[CH2:35]>C(Cl)Cl>[C:33]([N:16]1[CH2:17][CH2:18][C@H:14]([NH:13][C:11]2[C:12]3[C:7](=[CH:6][CH:5]=[CH:4][C:3]=3[F:2])[CH:8]=[C:9]([C:19]3[NH:23][C:22](=[O:24])[NH:21][N:20]=3)[N:10]=2)[CH2:15]1)(=[O:36])[CH:34]=[CH2:35]

Participants

5

Reactant 3

HCID 79372,6-Lutidine2×HCID 13140Acryloyl chloride2×HCID 136596990HCID 136596990, compound

Product 1

HCID 136295067HCID 136295067, compoundYield 15.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent5×

Conditions

Temperature
-78 °C

Procedure

To a mixture of (S)-3-(8-fluoro-1-(pyrrolidin-3-ylamino)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one hydrochloride (250 mg, 0.71 mmol) in DCM (15 mL) was added a solution of 2,6-dimethylpyridine (192 mg, 1.8 mmol) in DCM (1 mL). Acryloyl chloride (135 mg, 1.5 mmol) in DCM (1.35 mL) was added dropwise via syringe at −78° C. The reaction mixture was stirred at −78° C. for 30 minutes. Additional 2,6-dimethylpyridine (32 mg, 0.3 mmol) in DCM (0.32 mL) was added followed by acryloyl chloride (45 mg, 0.50 mmol) in DCM (0.45 mL). The reaction mixture was stirred at −10° C. for 20 minutes. The reaction was quenched with MeOH (1 mL) and the mixture was concentrated under vacuum. The crude product was purified by preparative HPLC to give the title compound as a white solid (40.58 mg, 15.5%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.91 (s, 1H), 11.78 (s, 1H), 7.69-7.63 (m, 3H), 7.60-7.58 (m, 1H), 6.61-6.55 (m, 2H), 6.18-6.13 (m, 1H), 5.67-5.64 (m, 1H), 5.30-5.10 (m, 1H), 4.17-4.15 (m, 1H), 3.66-3.63 (m, 2H), 3.28-3.25 (m, 1H), 2.25-2.03 (m, 2H); ESI-MS m/z [M+H]+ 369.1.

Workup

  1. stirringThe reaction mixture was stirred at −10° C. for 20 minutes
  2. customThe reaction was quenched with MeOH (1 mL)
  3. concentrationthe mixture was concentrated under vacuum
  4. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-659e03dee68740de8d41e975f7666b52
Source dataset
uspto-grants-2016_08
Patent number
US09402841B2

Reaction notes

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