1,2-Dichloroethane → (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(1-(3-chlorophenyl)-2-(N-methyl-2-nitrophenylsulfonamido)ethyl)-2-fluorobenzamide

HRID 595963노트

반응식

HRID 595963 반응식
[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[C:16]([F:23])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:6][N:7]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.[NH2:38][C@@H:39]([C:55]1[CH:60]=[CH:59][CH:58]=[C:57]([Cl:61])[CH:56]=1)[CH2:40][N:41]([CH3:54])[S:42]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1[N+:51]([O-:53])=[O:52])(=[O:44])=[O:43]>CN(C=O)C.CCOC(C)=O>[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH:38][C@@H:39]([C:55]3[CH:60]=[CH:59][CH:58]=[C:57]([Cl:61])[CH:56]=3)[CH2:40][N:41]([CH3:54])[S:42]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=3[N+:51]([O-:53])=[O:52])(=[O:43])=[O:44])=[O:20])=[C:16]([F:23])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:9][CH2:10][O:11][CH2:12][CH2:13]2)=[CH:6][N:7]=1

참가 물질

7

반응물 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 1180447134-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoic acidHCID 118045765(S)-N-(2-amino-2-(3-chlorophenyl)ethyl)-N-methyl-2-nitrobenzenesulfonamide

생성물 1

HCID 118045707(S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(1-(3-chlorophenyl)-2-(N-methyl-2-nitrophenylsulfonamido)ethyl)-2-fluorobenzamide수율 82.2%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoic acid (1.55 g, 4.88 mmol) in DMF (16.28 mL) was added HOAt (0.997 g, 7.33 mmol), EDC (1.498 g, 7.82 mmol) DIEA (2.61 m l, 14.65 mmol) and (S)—N-(2-amino-2-(3-chlorophenyl)ethyl)-N-methyl-2-nitrobenzenesulfonamide (2.084 g, 5.13 mmol). The reaction mixture was stirred at room temperature for 3 h, and LCMS indicated the reaction was completed. The reaction mixture was diluted with EtOAc, and the organic was washed by sat.Na2CO3, water and brine, dried over Na2SO4, filtered off, and concentrated. The crude material was purified by flash chromatography eluting with 50% DCM/EtOAc (10% methanol) to provide (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(1-(3-chlorophenyl)-2-(N-methyl-2-nitrophenylsulfonamido)ethyl)-2-fluorobenzamide (2.68 g, 4.01 mmol, 82%). LCMS: 669.1 (MH+), 0.95 min.

후처리

  1. washthe organic was washed
  2. dry with materialNa2CO3, water and brine, dried over Na2SO4
  3. filtrationfiltered off
  4. concentrationconcentrated
  5. customThe crude material was purified by flash chromatography
  6. washeluting with 50% DCM/EtOAc (10% methanol)

출처 및 근거

ORD 기록
ord-2a1575761507484b800cbbf190d66cdb
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242996B2

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