Pyridine → HCID 117675707, compound

HRID 1526224Notes

Reaction equation

HRID 1526224 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.[N:44]1C=CC=C[CH:45]=1>>[C:8]([C:6]1[N:7]=[C:2]([C:45]#[N:44])[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

3

Reactant 2

HCID 1049PyridineHCID 117675697HCID 117675697, compound

Product 1

HCID 117675707HCID 117675707, compound

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 (500 mg) and pyridine (3 mL) was added cuprous cyanide (88 mg), followed by reacting at 140° C. for 3 hours. The reactant was left to be cooled, and then subjected to liquid separation by the addition of a mixed solvent of chloroform:methanol:28% aqueous ammonia (100:10:1) and a saturated aqueous sodium hydrogen carbonate solution. To the organic phase was added silica gel, 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=1:0:0-200:10:1) to obtain tert-butyl (3R)-3-{[5-carbamoyl-3-cyano-6-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazin-2-yl]amino}pyrrolidine-1-carboxylate (Preparation Example 317 a:154 mg), which is a low-polarity product, as a yellow amorphous substance and tert-butyl (3R)-3-{[3,5-dicarbamoyl-6-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazin-2-yl]amino}pyrrolidine-1-carboxylate (Preparation Example 317 b:130 mg), which is a high-polarity substance, as a brown amorphous substance.

Workup

  1. waitThe reactant was left
  2. temperatureto be cooled
  3. customsubjected to liquid separation by the addition of a mixed solvent of chloroform
  4. additionTo the organic phase was added silica gel
  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=1:0:0-200:10:1)

Sources & evidence

ORD record
ord-27cd14aa88da4ef8ab5a03445936834a
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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