1H-Benzotriazole-1-methanol → HCID 117667085, compound

HRID 1526256Notes

Reaction equation

HRID 1526256 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[N:10]=[C:11]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([N:27]3[CH2:32][CH2:31][CH:30]([N:33]4[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]4)[CH2:29][CH2:28]3)=[CH:23][CH:22]=2)[C:12]([C:17]([NH2:19])=[O:18])=[N:13][C:14]=1[CH2:15][CH3:16].N1(CO)C2C=CC=C[C:43]=2N=N1.C([O-])(=O)C.[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(OCC)(=O)C.O1CCCC1.C(O)C>[CH2:15]([C:14]1[N:13]=[C:12]([C:17]([NH2:19])=[O:18])[C:11]([NH:20][C:21]2[CH:22]=[CH:23][C:24]([N:27]3[CH2:28][CH2:29][CH:30]([N:33]4[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]4)[CH2:31][CH2:32]3)=[CH:25][CH:26]=2)=[N:10][C:9]=1[NH:8][C@@H:3]1[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]1[NH:1][CH3:43])[CH3:16]

Participants

8

Reactant 4

HCID 2241691H-Benzotriazole-1-methanolHCID 517045Sodium AcetateHCID 5049666Sodium triacetoxyborohydrideHCID 117666957HCID 117666957, compound

Product 1

HCID 117667085HCID 117667085, compoundYield 67.6%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 5-{[(1R,2S)-2-aminocyclohexyl]amino}-6-ethyl-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazine-2-carboxamide (62 mg), ethanol (5 mL), and tetrahydrofuran (3 mL) were added 1H-benzotriazol-1-yl methanol (18 mg) and sodium acetate (15 mg), followed by stirring at room temperature for 7 hours. Sodium triacetoxyborohydride (50 mg) was added thereto under ice-cooling, followed by stirring at room temperature for 12 hours. To the reactant were added ethyl acetate and a saturated aqueous sodium hydrogen carbonate solution, 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=500:10:1-200:10:1) to obtain 6-ethyl-5-{[(1R,2S)-2-(methylamino)cyclohexyl]amino}-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazine-2-carboxamide (43 mg) as a pale yellow solid.

Workup

  1. temperatureunder ice-cooling
  2. stirringby stirring at room temperature for 12 hours
  3. customa saturated aqueous sodium hydrogen carbonate solution, followed by liquid separation
  4. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=500:10:1-200:10:1)

Sources & evidence

ORD record
ord-8fb08838b323447fb98d31f23e57290b
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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