Ammonium Bromide → 2-(4-Cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)acetamide

HRID 1525873ノート

反応式

HRID 1525873 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][C:20]=4[F:35])[C:16]([OH:18])=O)[CH2:11][CH2:10]3)[O:7][CH2:6][C:5]2=[O:36])[CH2:3][CH2:2]1.Cl.C[N:39](C)CCCN=C=NCC.[Br-].[NH4+]>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: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][C:20]=4[F:35])[C:16]([NH2:39])=[O:18])[CH2:11][CH2:10]3)[O:7][CH2:6][C:5]2=[O:36])[CH2:2][CH2:3]1

参加物

6

反応物 3

HCID 25514Ammonium BromideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 712709422-(4-Cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)acetic acid

生成物 1

HCID 712707212-(4-Cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)acetamide収率 37.4%

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-(2-fluoro-4-(quinolin-7-yl)phenyl)acetic acid (0.257 mmol) in dichloromethane (2 mL) was treated with N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.386 mmol) and 4-(dimethylamino)pyridine (1.030 mmol) at room temperature. This mixture was stirred for ten minutes at which point ammonium bromide (0.309 mmol) was added. The reaction was allowed to stir at room temperature overnight. The reaction was then concentrated to dryness under a stream of nitrogen. The resulting crude product was purified by reverse phase HPLC (10-40% acetonitrile with 0.1% TFA/water with 0.1% TFA). Fractions containing the desired product were combined and the pH of the resulting mixture was adjusted to ˜10 with 30% w/v aq ammonium hydroxide. This mixture was concentrated to a minimal volume in vacuo and was extracted three times with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Lyophilization from water afforded the title product as a white solid (47 mg, 35%). MS(ES)+ m/e 489.5 [M+H]+.

後処理

  1. additionwas added
  2. concentrationThe reaction was then concentrated to dryness under a stream of nitrogen
  3. customThe resulting crude product was purified by reverse phase HPLC (10-40% acetonitrile with 0.1% TFA/water with 0.1% TFA)
  4. additionFractions containing the desired product
  5. concentrationThis mixture was concentrated to a minimal volume in vacuo
  6. extractionwas extracted three times with dichloromethane
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-911ac55738a246ea961efc9601fe5c1b
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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