Methylamine → 2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-N-methyl-2-(4-(quinolin-7-yl)phenyl)acetamide

HRID 1525852노트

반응식

HRID 1525852 반응식
[CH:1]1([N:4]2[CH2:9][C:8]3([CH2:14][CH2:13][N:12]([CH:15]([C:19]4[CH:24]=[CH:23][C:22]([C:25]5[CH:34]=[C:33]6[C:28]([CH:29]=[CH:30][CH:31]=[N:32]6)=[CH:27][CH:26]=5)=[CH:21][CH:20]=4)[C:16]([OH:18])=O)[CH2:11][CH2:10]3)[O:7][CH2:6][C:5]2=[O:35])[CH2:3][CH2:2]1.Cl.[CH3:37][N:38](C)CCCN=C=NCC.CN>ClCCl.CN(C)C1C=CN=CC=1>[CH:1]1([N:4]2[CH2:9][C:8]3([CH2:14][CH2:13][N:12]([CH:15]([C:19]4[CH:20]=[CH:21][C:22]([C:25]5[CH:34]=[C:33]6[C:28]([CH:29]=[CH:30][CH:31]=[N:32]6)=[CH:27][CH:26]=5)=[CH:23][CH:24]=4)[C:16]([NH:38][CH3:37])=[O:18])[CH2:11][CH2:10]3)[O:7][CH2:6][C:5]2=[O:35])[CH2:3][CH2:2]1

참가 물질

6

반응물 3

HCID 6329Methylamine2회HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2회HCID 712708152-(4-Cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(4-(quinolin-7-yl)phenyl)acetic acid

생성물 1

HCID 712708412-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-N-methyl-2-(4-(quinolin-7-yl)phenyl)acetamide수율 26%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

실험 절차

A solution of 2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(4-(quinolin-7-yl)phenyl)acetic acid (0.191 mmol) in dichloromethane (2 mL) was treated with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.286 mmol) and 4-(dimethylamino)pyridine (0.763 mmol) at room temperature. After stirring for 10 minutes, this mixture was treated with methanamine (2M in THF) (0.400 mmol). The reaction vessel was sealed and the reaction was allowed to stir at room temperature for 16 hours. At this point an additional portion of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.15 mmol) and methanamine (2M in THF) (0.400 mmol) was added and the solution was allowed to stir at room temperature for 3 hours. The reaction was concentrated under a nitrogen stream. Purification of the residue by reverse phase HPLC (5-35% acetonitrile with 0.1% TFA/water with 0.1% TFA) and then by silica gel chromatography (0-9% methanol/dichloromethane) followed by lyophilization from water with 10% acetonitrile (1 mL) afforded the title compound (26%) as a white solid. MS(ES)+ m/e 485.4 [M+H]+.

후처리

  1. customThe reaction vessel was sealed
  2. stirringto stir at room temperature for 16 hours
  3. stirringto stir at room temperature for 3 hours
  4. concentrationThe reaction was concentrated under a nitrogen stream
  5. customPurification of the residue by reverse phase HPLC (5-35% acetonitrile with 0.1% TFA/water with 0.1% TFA)

출처 및 근거

ORD 기록
ord-e85cb5bdef4d481a86db35559cd11f5e
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09084794B2

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