Hydrochloric Acid → AT-Iap

HRID 1475530ノート

反応式

HRID 1475530 の反応式
C(OC([N:8]1[CH2:13][C@H:12]([CH2:14][N:15]2[CH2:20][CH2:19][O:18][CH2:17][C@H:16]2[CH3:21])[N:11]([CH2:22][C:23]([N:25]2[C:33]3[C:28](=[N:29][CH:30]=[C:31]([CH2:34][C:35]4[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=4)[CH:32]=3)[C:27]([CH3:43])([CH3:42])[CH2:26]2)=[O:24])[CH2:10][C@H:9]1[CH3:44])=O)(C)(C)C.Cl>C(OCC)(=O)C.O1CCOCC1>[F:41][C:38]1[CH:39]=[CH:40][C:35]([CH2:34][C:31]2[CH:32]=[C:33]3[N:25]([C:23](=[O:24])[CH2:22][N:11]4[CH2:10][C@@H:9]([CH3:44])[NH:8][CH2:13][C@@H:12]4[CH2:14][N:15]4[CH2:20][CH2:19][O:18][CH2:17][C@H:16]4[CH3:21])[CH2:26][C:27]([CH3:43])([CH3:42])[C:28]3=[N:29][CH:30]=2)=[CH:36][CH:37]=1

参加物

5

反応物 2

HCID 313Hydrochloric AcidHCID 70980911(2R,5S)-4-{2-[6-(4-Fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 70980530AT-Iap収率 87.9%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

To a vigorously stirred solution of (2R,5S)-4-{2-[6-(4-fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (11.3 g, 18.5 mmol) in ethyl acetate (100 mL) at 20° C. was added a solution of HCl in dioxan (100 mL) and stirring was continued for 18 h. The resulting fine yellow precipitate was collected by filtration and dried in vacuo. This material was suspended in water (200 mL) and extracted with EtOAc (200 mL). The organic phase was washed with 0.1 M aqueous HCl (50 mL) and the combined aqueous extracts were cooled in an ice bath and basified by the dropwise addition of 5 M aqueous NaOH. Resulting mixture was extracted with DCM (4×60 mL) and the combined extracts were dried (Na2SO4) and evaporated in vacuo to give the title compound (8.29 g) as a colourless foam. 1H NMR and MS data were consistent with those obtained above for Example 262. IR vC═O 1685 cm−1.

後処理

  1. filtrationThe resulting fine yellow precipitate was collected by filtration
  2. customdried in vacuo
  3. extractionextracted with EtOAc (200 mL)
  4. washThe organic phase was washed with 0.1 M aqueous HCl (50 mL)
  5. temperaturethe combined aqueous extracts were cooled in an ice bath
  6. additionbasified by the dropwise addition of 5 M aqueous NaOH
  7. customResulting mixture
  8. extractionwas extracted with DCM (4×60 mL)
  9. dry with materialthe combined extracts were dried (Na2SO4)
  10. customevaporated in vacuo

出典と根拠

ORDレコード
ord-a3ff2a94b52c4aaf89638af83f55a07d
出典データセット
uspto-grants-2015_04
特許番号
US09018214B2

反応ノート

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