1-Methylpiperazine → HCID 178492206, compound

HRID 869279Notes

Reaction equation

HRID 869279 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]([NH2:10])=[O:9])[C:5]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([N:20]3[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]3)[CH:13]=2)=[N:4][C:3]=1[NH:27][C@H:28]1[CH2:33][CH2:32][C@H:31]([OH:34])[CH2:30][CH2:29]1.[CH3:35][N:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+].C(OCC)(=O)C.C(OC(C)C)(C)C>ClCCCl>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([NH2:10])=[O:9])[C:5]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([N:20]3[CH2:21][CH2:22][CH:23]([N:39]4[CH2:40][CH2:41][N:36]([CH3:35])[CH2:37][CH2:38]4)[CH2:24][CH2:25]3)[CH:13]=2)=[N:4][C:3]=1[NH:27][C@H:28]1[CH2:29][CH2:30][C@H:31]([OH:34])[CH2:32][CH2:33]1

Participants

7

Reactant 5

HCID 531671-MethylpiperazineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 22281796Diisopropylether ethyl acetateHCID 178492207HCID 178492207, compound

Product 1

HCID 178492206HCID 178492206, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a mixture of 6-chloro-5-[(trans-4-hydroxycyclohexyl)amino]-3-{[4-methoxy-3-(4-oxopiperidin-1-yl)phenyl]amino}pyrazine-2-carboxamide (Example 495) (0.346 mg), N-methylpiperazine (0.12 mL) and 1,2-dichloroethane (10 mL), sodium triacetoxyborohydride (225 mg) was added and stirred at room temperature for 5 hours. After addition of saturated aqueous sodium hydrogen carbonate, the reaction liquid was extracted with chloroform, and the organic layer was washed with saturated aqueous sodium chloride. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; chloroform:methanol:saturated aqueous ammonia=100:0:0 to 20:1:0.1) to give a crude product. The crude product was solidified with ethyl acetate-diisopropyl ether and then washed with ethyl acetate to give 6-chloro-5-[(trans-4-hydroxycyclohexyl)amino]-3-({4-methoxy-3-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazine-2-carboxamide (39 mg) as a light yellow solid.

Workup

  1. additionwas added
  2. customthe reaction liquid
  3. extractionwas extracted with chloroform
  4. washthe organic layer was washed with saturated aqueous sodium chloride
  5. dry with materialAfter drying over anhydrous sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (eluent; chloroform:methanol:saturated aqueous ammonia=100:0:0 to 20:1:0.1)
  8. customto give a crude product
  9. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-a4df079c78374b91837573477375d9f0
Source dataset
uspto-grants-2015_03
Patent number
US08969336B2

Reaction notes

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