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

HRID 880346ノート

反応式

HRID 880346 の反応式
[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.[Cl:16][C:17]1[N:22]=[CH:21][N:20]=[C:19]([C:23](Cl)=[O:24])[CH:18]=1>C(Cl)Cl>[Cl:16][C:17]1[N:22]=[CH:21][N:20]=[C:19]([C:23]([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:24])[CH:18]=1

参加物

4

反応物 2

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

生成物 1

HCID 90241529(S)-6-chloro-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-4-carboxamide収率 49%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
10 °C

実験手順

To a stirred mixture of (S)-1-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (300 g, 1.46 mol), and TEA (300 g, 3 mol) in DCM (4 L) was added 6-chloropyrimidine-4-carbonyl chloride (250 g in 2 L of DCM) slowly at −60° C. over 1 h. After the addition was complete, the mixture was then allowed to warm to 10° C. Stirring was continued for 1 h, at which time TLC showed the reaction was completed. The reaction was quenched by addition of water (2 L). The organic phase was collected, dried (Na2SO4) and evaporated. The residue was purified by flash chromatography (EtOAc˜DCM:MeOH=10:1) to give the desired product as a pale yellow solid. Four batches were run in parallel and produced a combined product weight of 970 g, yield: 49%. 1H NMR (400 MHz, MeOD-d4) δ 8.73 (d, J=1.0 Hz, 1H), 8.07 (d, J=1.2 Hz, 1H), 7.17-7.06 (m, 3H), 7.00 (d, J=7.2 Hz, 1H), 5.51 (s, 1H), 4.12 (q, J=6.0 Hz, 1H), 3.74 (s, 2H), 3.64-3.53 (m, 2H), 2.94 (q, J=5.6 Hz, 2H), 2.92-2.81 (m, 2H), 2.78-2.64 (m, 2H); LCMS (m/z): 347.2 [M+H]+

後処理

  1. additionAfter the addition
  2. customThe reaction was quenched by addition of water (2 L)
  3. customThe organic phase was collected
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customThe residue was purified by flash chromatography (EtOAc˜DCM:MeOH=10:1)

出典と根拠

ORDレコード
ord-274aeed34b9b4258b31b263e23f9753f
出典データセット
uspto-grants-2015_03
特許番号
US08993555B2

反応ノート

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