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 2234319노트

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HRID 2234319 반응식
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]

참가 물질

6

반응물 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)-one2회HCID 643214944-amino-3-chloro-N-(1-ethyl-4-piperidyl)benzamide2회

생성물 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)benzamide수율 20%

시약·촉매·용매 1

HCID 79104-Methyl-2-Pentanol용매

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온도
160 °C

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-8e710f88596e45e2bb9f11ac9c554c90
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07709471B2

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