2,4,6-Trimethylpyridine → (S)-tert-butyl 2-(4-chlorophenyl)-3-(isoquinolin-6-ylamino)-3-oxopropylcarbamate

HRID 1482737ノート

反応式

HRID 1482737 の反応式
[C:1]([O:5][C:6]([NH:8][CH2:9][C@H:10]([C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC1C=C(C)C=C(C)N=1.ClC(OC(C)(C)C(Cl)(Cl)Cl)=O.[NH2:41][C:42]1[CH:43]=[C:44]2[C:49](=[CH:50][CH:51]=1)[CH:48]=[N:47][CH:46]=[CH:45]2.C([O-])(O)=O.[Na+]>CN(C=O)C>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([C@H:10]([C:11]([NH:41][C:42]2[CH:43]=[C:44]3[C:49](=[CH:50][CH:51]=2)[CH:48]=[N:47][CH:46]=[CH:45]3)=[O:13])[CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:15][CH:16]=1

参加物

7

反応物 5

HCID 79532,4,6-TrimethylpyridineHCID 516892Sodium BicarbonateHCID 5889916-AminoisoquinolineHCID 51066062,2,2-Trichloro-tert-butyl chloroformateHCID 29947824HCID 29947824、化合物

生成物 1

HCID 90412140(S)-tert-butyl 2-(4-chlorophenyl)-3-(isoquinolin-6-ylamino)-3-oxopropylcarbamate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒3 回

反応条件

温度
0 °C

実験手順

To (S)-3-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)propanoic acid (28) (8.5 g, 28.4 mmol) in DMF cooled to 0° C. was added 2,4,6-trimethylpyridine and 2,2,2-trichloro-1,1-dimethylethyl chloroformate in DMF. Then, 6-aminoisoquinoline in DMF was added and the solution stirred for 2 h at 0° C. The mixture was poured into NaHCO3 (sat) and extracted with EtOAc. The organic layers were washed with H2O, dried (Na2SO4), filtered and evaporated to give crude 29. Column chromatography (30% EtOAc-Hexanes) and recrystallization (EtOAc/Hexanes) gave pure (S)-tert-butyl 2-(4-chlorophenyl)-3-(isoquinolin-6-ylamino)-3-oxopropylcarbamate (29, 7.8 g, 64%, >99% S enantiomer).

後処理

  1. extractionextracted with EtOAc
  2. washThe organic layers were washed with H2O
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto give crude 29
  7. customColumn chromatography (30% EtOAc-Hexanes) and recrystallization (EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-68c478e9f6394efbafce932177535957
出典データセット
uspto-grants-2016_08
特許番号
US09415043B2

反応ノート

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