Water → Tert-butyl 4-{3-[(3R)-3-{[(1S)-1-(5-(4-cyano-3-fluorobenzyloxy)pyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

HRID 526352ノート

反応式

HRID 526352 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24](=[O:39])[NH:25][C@H:26]([C:32]3[CH:33]=[N:34][CH:35]=[C:36]([OH:38])[CH:37]=3)[CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH2:19]2)=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:43][C:44]1[CH:51]=[CH:50][C:47]([C:48]#[N:49])=[C:46]([F:52])[CH:45]=1.O>CN(C=O)C.[Cl-].[Na+].O.C(OCC)(=O)C>[C:48]([C:47]1[CH:50]=[CH:51][C:44]([CH2:43][O:38][C:36]2[CH:37]=[C:32]([C@@H:26]([NH:25][C:24]([C@@H:20]3[CH2:21][CH2:22][CH2:23][N:18]([C:16](=[O:17])[CH2:15][CH2:14][CH:11]4[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:13][CH2:12]4)[CH2:19]3)=[O:39])[CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH:33]=[N:34][CH:35]=2)=[CH:45][C:46]=1[F:52])#[N:49]

参加物

8

反応物 4

HCID 962WaterHCID 24758Sodium hydrideHCID 27784664-Cyano-3-fluorobenzyl bromideHCID 71259055tert-butyl-4-{3-[(3R)-3-{[(1S)-1-(5-hydroxypyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

生成物 1

HCID 71258934Tert-butyl 4-{3-[(3R)-3-{[(1S)-1-(5-(4-cyano-3-fluorobenzyloxy)pyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate収率 4.5%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
0 °C

実験手順

To tert-butyl-4-{3-[(3R)-3-{[(1S)-1-(5-hydroxypyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (example 5e, 200 mg, 0.37 mmol) in DMF (5 mL) was added sodium hydride (60%, 9.6 mg, 0.24 mmol) and the mixture was cooled to 0° C. 4-(Bromomethyl)-2-fluorobenzonitrile (70.5 mg, 0.33 mmol) in DMF (3 mL) was added while stirring and the mixture was warmed to room temperature. After one hour water, brine and ethyl acetate were added. Phases were separated and the aqueous phase was extracted with ethyl acetate. The combined extracts were dried over sodium sulfate and concentrated in vacuum. The residue was purified by preparative HPLC to yield 10 mg of tert-butyl 4-{3-[(3R)-3-{[(1S)-1-{5-[(4-cyano-3-fluorobenzyl)oxy]pyridin-3-yl}-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate.

後処理

  1. temperaturethe mixture was warmed to room temperature
  2. customPhases were separated
  3. extractionthe aqueous phase was extracted with ethyl acetate
  4. dry with materialThe combined extracts were dried over sodium sulfate
  5. concentrationconcentrated in vacuum
  6. customThe residue was purified by preparative HPLC

出典と根拠

ORDレコード
ord-37f3413513324f96983a8a58e9d413dd
出典データセット
uspto-grants-2016_05
特許番号
US09345793B2

反応ノート

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