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 1525852ノート

反応式

HRID 1525852 の反応式
[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

参加物

6

反応物 3

HCID 6329Methylamine2 回HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2 回HCID 712708152-(4-Cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(4-(quinolin-7-yl)phenyl)acetic acid

生成物 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)acetamide収率 26%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-e85cb5bdef4d481a86db35559cd11f5e
出典データセット
uspto-grants-2015_07
特許番号
US09084794B2

反応ノート

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