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Cesium carbonate → (3-Carbamoyl-1-{2-[(2S,4R)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl}-1H-indol-6-yloxy)-acetic acid methyl ester

HRID 1527573
ノート
印刷プレビュー

反応式

HRID 1527573 の反応式
[Cl:1][C:2]1[C:3]([F:34])=[C:4]([CH:31]=[CH:32][CH:33]=1)[CH2:5][NH:6][C:7]([C@@H:9]1[CH2:13][C@@H:12]([F:14])[CH2:11][N:10]1[C:15](=[O:30])[CH2:16][N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([OH:26])[CH:24]=2)[C:19]([C:27]([NH2:29])=[O:28])=[CH:18]1)=[O:8].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:42][C:43]([O:45][CH3:46])=[O:44]>CS(C)=O>[CH3:46][O:45][C:43](=[O:44])[CH2:42][O:26][C:23]1[CH:24]=[C:25]2[C:20]([C:19]([C:27](=[O:28])[NH2:29])=[CH:18][N:17]2[CH2:16][C:15]([N:10]2[CH2:11][C@H:12]([F:14])[CH2:13][C@H:9]2[C:7](=[O:8])[NH:6][CH2:5][C:4]2[CH:31]=[CH:32][CH:33]=[C:2]([Cl:1])[C:3]=2[F:34])=[O:30])=[CH:21][CH:22]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 10796Cesium carbonateHCID 60984Methyl bromoacetateHCID 682831451-{2-[(2S,4R)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl}-6-hydroxy-1H-indole-3-carboxylic acid amide

生成物 1

HCID 68283320(3-Carbamoyl-1-{2-[(2S,4R)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl}-1H-indol-6-yloxy)-acetic acid methyl ester

試薬・触媒・溶媒 1

HCID 679
Dimethyl Sulfoxide
溶媒

実験手順

A solution of 1-{2-[(2S,4R)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl}-6-hydroxy-1H-indole-3-carboxylic acid amide Example 578 (140 mg, 0.285 mmol) in DMSO (3 mL) was treated with Cs2CO3 (0.28 g, 0.85 mmol). The mixture was stirred at RT for 5 min, followed by addition of methyl 2-bromoacetate (0.039 mL, 0.428 mmol) and stirring at RT for 4 h. The mixture was partitioned between water and CH2Cl2, and the organic phase was washed twice with brine (the combined aqueous washings were filtered and the solid thus obtained was dried in vacuo to give an aliquot of the title compound), dried (phase separator) and concentrated under reduced pressure. Purification by preparative HPLC (SunFire C18-ODB, 5 μm, 30×100 mm, eluent: 20-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min) afforded after lyophilization of the purified fractions the title compound as a white solid. MS: 563 [M+H]+; tR (HPLC conditions c): 4.17 min.

後処理

  1. stirringstirring at RT for 4 h
  2. customThe mixture was partitioned between water and CH2Cl2
  3. washthe organic phase was washed twice with brine (the combined aqueous washings
  4. filtrationwere filtered
  5. customthe solid thus obtained
  6. customwas dried in vacuo

出典と根拠

ORDレコード
ord-1ea71285de464dc5985b71d00cbc3a92
出典データセット
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09085555B2

反応ノート

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