1-Hydroxybenzotriazole → 7-{4-[3-(tert-Butyldimethylsilanyloxy)propyl]thiazol-2-yl}-6-[cyclopropyl-(2,3-dichlorobenzyl)carbamoyl]-3,9-diazabicyclo[3.3.1]non-6-ene-3,9-dicarboxylic acid di-tert-butyl ester

HRID 1096848노트

반응식

HRID 1096848 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[N:16]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:10]([CH2:11][C:12]([C:27]3[S:28][CH:29]=[C:30]([CH2:32][CH2:33][CH2:34][O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])[N:31]=3)=[C:13]2[C:24]([OH:26])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:43]1([NH:46][CH2:47][C:48]2[CH:53]=[CH:52][CH:51]=[C:50]([Cl:54])[C:49]=2[Cl:55])[CH2:45][CH2:44]1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[N:16]([C:17]([O:19][C:20]([CH3:23])([CH3:21])[CH3:22])=[O:18])[CH:10]([CH2:11][C:12]([C:27]3[S:28][CH:29]=[C:30]([CH2:32][CH2:33][CH2:34][O:35][Si:36]([C:39]([CH3:41])([CH3:42])[CH3:40])([CH3:38])[CH3:37])[N:31]=3)=[C:13]2[C:24](=[O:26])[N:46]([CH:43]2[CH2:44][CH2:45]2)[CH2:47][C:48]2[CH:53]=[CH:52][CH:51]=[C:50]([Cl:54])[C:49]=2[Cl:55])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

참가 물질

8

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 834599Cyclopropyl-(2,3-dichloro-benzyl)-amineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 685745837-{4-[3-(tert-Butyldimethylsilanyloxy)propyl]thiazol-2-yl}-3,9-diazabicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester

생성물 1

HCID 685697247-{4-[3-(tert-Butyldimethylsilanyloxy)propyl]thiazol-2-yl}-6-[cyclopropyl-(2,3-dichlorobenzyl)carbamoyl]-3,9-diazabicyclo[3.3.1]non-6-ene-3,9-dicarboxylic acid di-tert-butyl ester수율 34.4%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매2회

실험 절차

A mixture of compound D2 (2.87 g, 4.60 mmol), cyclopropyl-(2,3-dichlorobenzyl)amine (prepared from 2,3-dichlorobenzaldehyde and cyclopropylamine by reductive amination, 2.49 g, 11.5 mmol), DIPEA (3.15 mL, 18.4 mmol), DMAP (140 mg, 1.15 mmol), HOBt (932 mg, 6.90 mmol) and EDC.HCl (2.65 g, 13.8 mmol) in CH2Cl2 (50 mL) was stirred at rt for 6 days. The mixture was diluted with more CH2Cl2, and washed with aq. 1M HCl (3×) and aq. sat. NaHCO3 (1×). The org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 1:5→1:3→1:2→1:1→3:2) yielded the title compound (1.30 g, 34%). LC-MS: tR=1.33 min, ES+: 821.54.

후처리

  1. washwashed with aq. 1M HCl (3×) and aq. sat. NaHCO3 (1×)
  2. dry with materialextracts were dried over MgSO4
  3. filtrationfiltered
  4. customthe solvents were removed under reduced pressure
  5. customPurification of the residue by FC (EtOAc/heptane 1:5→1:3→1:2→1:1→3:2)

출처 및 근거

ORD 기록
ord-67681ce66cc34f87bd615e1f2f976704
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08138340B2

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