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

HRID 1482737노트

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HRID 1482737 반응식
[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

참가 물질

7

반응물 5

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매3회

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온도
0 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-68c478e9f6394efbafce932177535957
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09415043B2

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