Sodium Carbonate → HCID 131733158, compound

HRID 1526258Notes

Reaction equation

HRID 1526258 reaction equation
Br[C:2]1[C:3]([NH:31][C@@H:32]2[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33]2)=[N:4][C:5]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][CH:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)=[CH:14][CH:13]=2)=[C:6]([C:8](=[O:10])[NH2:9])[N:7]=1.C(=O)([O-])[O-].[Na+].[Na+].O1[CH2:55][CH2:54][O:53][CH2:52]C1>>[C:8]([C:6]1[N:7]=[C:2]([C:14]2[CH:15]=[CH:16][CH:55]=[C:54]([O:53][CH3:52])[C:13]=2[C:12]#[N:11])[C:3]([NH:31][C@@H:32]2[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33]2)=[N:4][C:5]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH2:23][CH2:22][CH:21]([N:24]3[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]3)[CH2:20][CH2:19]2)=[CH:14][CH:13]=1)(=[O:10])[NH2:9]

Participants

4

Reactant 3

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 117675697HCID 117675697, compound

Product 1

HCID 131733158HCID 131733158, compound

Conditions

Temperature
100 °C

Procedure

To a mixture of tert-butyl (3R)-3-{[3-bromo-5-carbamoyl-6-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazin-2-yl]amino}pyrrolidine-1-carboxylate (220 mg), neopentyl glycol ester 2-cyano-3-methoxyphenylborate (164 mg), and tetrakistriphenylphosphine palladium (0) (39 mg), dioxane (8.8 mL) was added a 2 M aqueous sodium carbonate solution (836 μL), followed by stirring at 100° C. for 3 hours under an argon atmosphere. After leaving to be cooled, the mixture was subjected to liquid separation by the addition of ethyl acetate and water. The organic phase was dried over anhydrous magnesium sulfate and then the solvent was evaporated. The obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-200:10:1) to obtain tert-butyl (3R)-3-{[5-carbamoyl-3-(2-cyano-3-methoxyphenyl)-6-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazin-2-yl]amino}pyrrolidine-1-carboxylate (208 mg).

Workup

  1. customAfter leaving
  2. temperatureto be cooled
  3. customthe mixture was subjected to liquid separation by the addition of ethyl acetate and water
  4. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated
  6. customThe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-200:10:1)

Sources & evidence

ORD record
ord-7d4e1b20bad44957b4edd5038d667bea
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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