Triethylamine → (S)-6-chloro-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-4-carboxamide

HRID 880331Notes

Reaction equation

HRID 880331 reaction equation
[NH2:1][CH2:2][C@H:3]([OH:15])[CH2:4][N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6]1.CCN(CC)CC.[Cl:23][C:24]1[N:29]=[CH:28][N:27]=[C:26]([C:30](Cl)=[O:31])[CH:25]=1>C(Cl)Cl>[Cl:23][C:24]1[N:29]=[CH:28][N:27]=[C:26]([C:30]([NH:1][CH2:2][C@H:3]([OH:15])[CH2:4][N:5]2[CH2:14][CH2:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[CH2:6]2)=[O:31])[CH:25]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 184220986-Chloropyrimidine-4-carbonyl chlorideHCID 25312355(S)-1-Amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol

Product 1

HCID 90241529(S)-6-chloro-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-4-carboxamideYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred and cooled (0° C.) solution of (S)-1-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (7.15 g, 34.7 mmol) and Et3N (14.0 g, 138.8 mmol) in DCM (100 mL) was added 6-chloropyrimidine-4-carbonyl chloride (5.5 g, 34.7 mmol). After addition, the resulting mixture was stirred at 25° C. for 16 h, at which time LCMS showed the completion of the reaction. The solvent was evaporated and the residue purified by flash chromatography to give the (S)-6-chloro-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-4-carboxamide (7.2 g, yield: 60%). LCMS (m/z): 347.0 [M+H]+

Workup

  1. additionAfter addition
  2. stirringthe resulting mixture was stirred at 25° C. for 16 h, at which time LCMS
  3. customthe completion of the reaction
  4. customThe solvent was evaporated
  5. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-c488a20bdf844243a744a59db7811d96
Source dataset
uspto-grants-2015_03
Patent number
US08993555B2

Reaction notes

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