1,2-Dichloroethane → HCID 117675638, compound

HRID 1526215Notes

Reaction equation

HRID 1526215 reaction equation
[C:1]([C:4]1[N:5]=[C:6]([Cl:38])[C:7]([NH:25][C@@H:26]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27]2)=[N:8][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][C:20](=O)[CH2:19][CH2:18]2)=[C:13]([CH3:24])[CH:12]=1)(=[O:3])[NH2:2].[CH3:39][N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1.ClCCCl.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl>[C:1]([C:4]1[N:5]=[C:6]([Cl:38])[C:7]([NH:25][C@@H:26]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[CH2:27]2)=[N:8][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][CH:20]([N:43]3[CH2:44][CH2:45][N:40]([CH3:39])[CH2:41][CH2:42]3)[CH2:19][CH2:18]2)=[C:13]([CH3:24])[CH:12]=1)(=[O:3])[NH2:2]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 531671-Methylpiperazine2×HCID 5049666Sodium triacetoxyborohydrideHCID 117675639HCID 117675639, compound

Product 1

HCID 117675638HCID 117675638, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a mixture of tert-butyl (3R)-3-[(5-carbamoyl-3-chloro-6-{[3-methyl-4-(4-oxopiperidin-1-yl)phenyl]amino}pyrazin-2-yl)amino]pyrrolidine-1-carboxylate (578 mg), 1-methylpiperazine (175 μL), and 1,2-dichloroethane (8.67 mL) was added sodium triacetoxyborohydride (338 mg), followed by stirring at room temperature for 3 hours. To the reactant was added 1-methylpiperazine (82 μL), followed by stirring at room temperature for 4 hours. To the reactant were added chloroform and a saturated aqueous sodium hydrogen carbonate solution, and followed by liquid separation. The organic phase was dried over anhydrous magnesium sulfate and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-300:10:1) to obtain tert-butyl (3R)-3-{[5-carbamoyl-3-chloro-6-({3-methyl-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazin-2-yl]amino}pyrrolidine-1-carboxylate (560 mg) as a yellow amorphous substance.

Workup

  1. stirringby stirring at room temperature for 4 hours
  2. customa saturated aqueous sodium hydrogen carbonate solution, and followed by liquid separation
  3. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-300:10:1)

Sources & evidence

ORD record
ord-26bac9c1bdad44498ebb416394ccb108
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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