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Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 2-[5-chloro-2-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide

HRID 1688144
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HRID 1688144 반응식
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:11][N:10]([CH3:12])[CH2:9][C:8](=[O:13])[NH:7][C:6]=2[CH:14]=1.Cl[C:16]1[N:21]=[C:20]([NH:22][C:23]2[CH:32]=[CH:31][CH:30]=[CH:29][C:24]=2[C:25]([NH:27][CH3:28])=[O:26])[C:19]([Cl:33])=[CH:18][N:17]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>CC(O)C.Cl.O1CCOCC1>[Cl:33][C:19]1[C:20]([NH:22][C:23]2[CH:32]=[CH:31][CH:30]=[CH:29][C:24]=2[C:25]([NH:27][CH3:28])=[O:26])=[N:21][C:16]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[CH2:11][N:10]([CH3:12])[CH2:9][C:8](=[O:13])[NH:7][C:6]=3[CH:14]=2)=[N:17][CH:18]=1
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참가 물질

6

반응물 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamideHCID 672638558-Amino-4-methyl-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one

생성물 1

HCID 251592822-[5-chloro-2-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide수율 16%

시약·촉매·용매 2

HCID 204431481,4-Dioxane hydrochloride촉매
HCID 3776Isopropanol용매

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온도
120 °C

실험 절차

A mixture of 8-amino-4-methyl-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one and 2-(2,5-dichloropyrimidin-4-ylamino)-N-methylbenzamide (22 mg, 0.08 mmol), and camphorsulfonic acid (17.4 mg, 0.08 mmol) were heated in IPA (3 mL) at 120° C. for 16 hours. The mixture was heated for another 2.5 hours at 120° C. after the addition of 10 drops of 4 N HCl/dioxane. Concentration and chromatography on preparative TLC with methylene chloride and methanol (100:8) followed by semi-preparative HPLC gave 5 mg of 2-[5-chloro-2-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide (16% yield): 1H NMR (300 MHz, CD3OD) δ 8.7 (d, 1H), 8.13 (s, 1H), 7.96 (s, 1H), 7.67 (m, 3H), 7.4 (m, 1H), 7.2 (m, 1H), 3.95 (s, 1H), 3.7 (s, 1H), 3.6 (s, 2H), 2.95 (s, 3H), 2.53 (s, 3H); MS (m/e): 452.2 (M+1).

후처리

  1. concentrationConcentration and chromatography on preparative TLC with methylene chloride and methanol (100:8)

출처 및 근거

ORD 기록
ord-7386decdf51d4f65bb08eecfc6869ca1
출처 데이터셋
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08148391B2

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