2,6-Lutidine → HCID 136297920, compound

HRID 1476876Notes

Reaction equation

HRID 1476876 reaction equation
Cl.[F:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[C:11]([O: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]([O: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-LutidineHCID 13140Acryloyl chlorideHCID 136597055HCID 136597055, compound

Product 1

HCID 136297920HCID 136297920, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-40 °C

Procedure

To a mixture of (S)-3-(8-fluoro-1-(pyrrolidin-3-yloxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one hydrochloride (80 mg, 0.22 mmol) in DCM (5 mL) was added 2,6-dimethylpyridine (70 mg, 0.6 mmol). The mixture was cooled to −40° C. Acryloyl chloride (25 mg, 0.28 mmol) was added and the reaction mixture was warmed to 0° C. over a 30 minute period. The reaction was quenched with MeOH (5 mL) and the mixture concentrated in vacuo. The crude product was purified by preparative HPLC to give the title compound (43 mg, 54%). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.07 (s, 1H), 11.88 (s, 1H), 8.01 (s, 1H), 7.85-7.83 (d, J=8 Hz, 1H), 7.78-7.76 (t, J=4 Hz, 1H), 7.39 (m, 1H), 6.67-6.64 (m, 1H), 6.19-6.14 (m, 2H), 5.72-5.66 (m, 1H), 4.06 (m, 0.5H), 3.85-3.58 (m, 3.5H), 2.29-2.25 (m, 2H).

Workup

  1. temperaturethe reaction mixture was warmed to 0° C. over a 30 minute period
  2. customThe reaction was quenched with MeOH (5 mL)
  3. concentrationthe mixture concentrated in vacuo
  4. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-c7c20935442b448ba24ea8243a6d5d44
Source dataset
uspto-grants-2016_08
Patent number
US09402841B2

Reaction notes

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