Methanol → 3-chloro-4-(9'-cyclopentyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepine]-2'-ylamino)-N-(1-ethylpiperidin-4-yl)benzamide

HRID 2234319ノート

反応式

HRID 2234319 の反応式
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:6]([CH3:21])[C:7](=[O:20])[C:8]3([CH2:19][CH2:18]3)[CH2:9][N:10]([CH:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[C:11]=2[N:12]=1.[NH2:22][C:23]1[CH:39]=[CH:38][C:26]([C:27]([NH:29][CH:30]2[CH2:35][CH2:34][N:33]([CH2:36][CH3:37])[CH2:32][CH2:31]2)=[O:28])=[CH:25][C:24]=1[Cl:40].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.CO>CC(C)CC(O)C>[Cl:40][C:24]1[CH:25]=[C:26]([CH:38]=[CH:39][C:23]=1[NH:22][C:2]1[N:3]=[CH:4][C:5]2[N:6]([CH3:21])[C:7](=[O:20])[C:8]3([CH2:18][CH2:19]3)[CH2:9][N:10]([CH:13]3[CH2:14][CH2:15][CH2:16][CH2:17]3)[C:11]=2[N:12]=1)[C:27]([NH:29][CH:30]1[CH2:31][CH2:32][N:33]([CH2:36][CH3:37])[CH2:34][CH2:35]1)=[O:28]

参加物

6

反応物 4

HCID 887MethanolHCID 521998p-Toluenesulfonic acid monohydrateHCID 579699392-chloro-9-cyclopentyl-8,9-dihydro-5-methylspiro[5H-pyrimido[4,5-b][1,4]diazepine-7,1'-cyclopropan]-6(7H)-one2 回HCID 643214944-amino-3-chloro-N-(1-ethyl-4-piperidyl)benzamide2 回

生成物 1

HCID 686844003-chloro-4-(9'-cyclopentyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepine]-2'-ylamino)-N-(1-ethylpiperidin-4-yl)benzamide収率 20%

試薬・触媒・溶媒 1

HCID 79104-Methyl-2-Pentanol溶媒

反応条件

温度
160 °C

実験手順

2′-chloro-9′-cyclopentyl-5′-methyl-8′,9′-dihydrospiro[cyclopropane-1,7′-pyrimido[5,4-b][1,4]diazepin]-6′(5′H)-one (Intermediate 130; 108 mg, 0.35 mmol) 4-amino-3-chloro-N-(1-ethyl-4-piperidyl)benzamide (Intermediate 212; 118 mg, 0.42 mmol), and p-toluenesulphonic acid monohydrate (133 mg, 0.7 mmol) were combined in 4-methyl-2-pentanol (4 mL) and heated by microwave irradiation at 160° C. for 1 hour. The reaction mixture was loaded onto to an SCX cartridge (10 g) pre-wet with methanol, then washed with methanol and eluted with methanolic ammonia. Product containing fractions were combined and evaporated and the resultant material purified by base modified reverse phase preparative HPLC to yield the title compound as a white solid (38 mg, 20%).

後処理

  1. washwashed with methanol
  2. washeluted with methanolic ammonia
  3. additionProduct containing fractions
  4. customevaporated
  5. customthe resultant material purified by base modified reverse phase preparative HPLC

出典と根拠

ORDレコード
ord-8e710f88596e45e2bb9f11ac9c554c90
出典データセット
uspto-grants-2010_05
特許番号
US07709471B2

反応ノート

読み込み中…