Ethanol → tert-butyl (3R)-3-{[5-carbamoyl-3-isopropyl-6-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazin-2-yl]oxy}pyrrolidine-1-carboxylate

HRID 1526194Notes

Reaction equation

HRID 1526194 reaction equation
[C:1]([C:4]1[N:5]=[C:6]([C:43]([CH3:45])=[CH2:44])[C:7]([O:30][C@@H:31]2[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32]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:23]3[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]3)[CH2:19][CH2:18]2)=[CH:13][CH:12]=1)(=[O:3])[NH2:2].C(O)C>[Pd].O1CCCC1>[C:1]([C:4]1[N:5]=[C:6]([CH:43]([CH3:45])[CH3:44])[C:7]([O:30][C@@H:31]2[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:41])([CH3:40])[CH3:42])=[O:37])[CH2:32]2)=[N:8][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:18][CH2:19][CH:20]([N:23]3[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]3)[CH2:21][CH2:22]2)=[CH:13][CH:12]=1)(=[O:3])[NH2:2]

Participants

5

Reactant 2

HCID 702EthanolHCID 117675492tert-butyl (3R)-3-{[5-carbamoyl-6-({-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-3-(prop-1-en-2-yl)pyrazin-2-yl]oxy}pyrrolidine-1-carboxylate

Product 1

HCID 117675494tert-butyl (3R)-3-{[5-carbamoyl-3-isopropyl-6-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazin-2-yl]oxy}pyrrolidine-1-carboxylateYield 84.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of tert-butyl (3R)-3-{[5-carbamoyl-6-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-3-(prop-1-en-2-yl)pyrazin-2-yl]oxy}pyrrolidine-1-carboxylate (300 mg), ethanol (6 mL), and tetrahydrofuran (6 mL) was added 10% palladium-supported carbon (50% wet product) (260 mg), followed by stirring at room temperature overnight under a hydrogen gas atmosphere (4 atm). The reaction mixture was filtered through celite, and then the solvent was evaporated under reduced pressure and washed with diisopropyl ether to obtain tert-butyl (3R)-3-{[5-carbamoyl-3-isopropyl-6-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazin-2-yl]oxy}pyrrolidine-1-carboxylate (253 mg) as a yellow solid.

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. customthe solvent was evaporated under reduced pressure
  3. washwashed with diisopropyl ether

Sources & evidence

ORD record
ord-e663965587234c8ab2ab08b66a04a2d2
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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