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 595963Notes

Reaction equation

HRID 595963 reaction equation
[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

Participants

7

Reactant 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

Product 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-fluorobenzamideYield 82.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-2a1575761507484b800cbbf190d66cdb
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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