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2,6-Lutidine → 3-[8-chloro-1-[[(3S)-1-prop-2-enoylpyrrolidin-3-yl]amino]isoquinolin-3-yl]-1,4-dihydro-1,2,4-triazol-5-one

HRID 1476906
Notes
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Reaction equation

HRID 1476906 reaction equation
Cl.[Cl: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[Cl: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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 13140Acryloyl chlorideHCID 136597068(S)-3-(8-chloro-1-(pyrrolidin-3-ylamino)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one hydrochloride

Product 1

HCID 1362867373-[8-chloro-1-[[(3S)-1-prop-2-enoylpyrrolidin-3-yl]amino]isoquinolin-3-yl]-1,4-dihydro-1,2,4-triazol-5-oneYield 52%

Reagents, catalysts & solvents 1

HCID 6344
Dichloromethane
Solvent

Conditions

Temperature
-40 °C

Procedure

To a mixture of (S)-3-(8-chloro-1-(pyrrolidin-3-ylamino)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one hydrochloride (100 mg, 0.3 mmol) in DCM (20 mL) was added 2,6-dimethylpyridine (97 mg, 0.91 mmol). The resulting mixture was cooled to −40° C. Acryloyl chloride (51 mg, 0.6 mmol, 10 mg/mL in dry DCM) was added dropwise and the mixture was stirred at −40° C. for 30 minutes. The reaction was subsequently quenched with MeOH (5 mL) and the mixture was concentrated in vacuo. The crude product was purified by preparative HPLC to give the title compound (57 mg, 52%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.91 (s, 1H), 11.80 (s, 1H), 7.85-7.83 (m, 1H), 7.61-7.59 (m, 3H), 7.49-7.47 (m, 1H), 6.6-6.5 (m, 1H), 6.17-6.13 (m, 1H), 5.67-5.63 (m, 1H), 5.18-5.16 (m, 1H), 4.18-4.17 (m, 0.5H), 3.69-3.65 (m, 0.5H), 3.42 (m, 0.5H), 3.32-3.31 (m, 1.5H), 2.31-2.29 (m, 1H), 2.04-2.01 (m, 1H); ESI-MS m/z [M+H]+ 385.1.

Workup

  1. customThe reaction was subsequently quenched with MeOH (5 mL)
  2. concentrationthe mixture was concentrated in vacuo
  3. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-88b9a72357b8415d92a756ca2ec6116c
Source dataset
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09402841B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes