Acetic Acid → 1-[4-(6-(Methylamino)purin-9-yl)phenyl]-3-[4-(4-methylpiperazin-1-ylmethyl)-3-(trifluoromethyl)phenyl]urea

HRID 1912866Notes

Reaction equation

HRID 1912866 reaction equation
C(OC(=O)[N:7]([C:9]1[N:17]=[CH:16][N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([CH:34]=O)=[C:30]([C:36]([F:39])([F:38])[F:37])[CH:29]=2)=[O:26])=[CH:20][CH:19]=1)[CH3:8])(C)(C)C.C(O)(=O)C.[CH3:45][N:46]1[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1.C([BH3-])#N.[Na+]>C(O)C>[CH3:8][NH:7][C:9]1[N:17]=[CH:16][N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[C:18]1[CH:19]=[CH:20][C:21]([NH:24][C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([CH2:34][N:49]3[CH2:50][CH2:51][N:46]([CH3:45])[CH2:47][CH2:48]3)=[C:30]([C:36]([F:37])([F:38])[F:39])[CH:29]=2)=[O:26])=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 5003444Sodium cyanoborohydrideHCID 59725906(9-{4-[3-(4-formyl-3-(trifluoromethyl)phenyl)ureido]phenyl}-9H-purin-6-yl)-methylcarbamic acid tert-butyl ester

Product 1

HCID 231552721-[4-(6-(Methylamino)purin-9-yl)phenyl]-3-[4-(4-methylpiperazin-1-ylmethyl)-3-(trifluoromethyl)phenyl]ureaYield 72.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

In 2 mL of ethanol, 40 mg (0.07 mmol) of (9-{4-[3-(4-formyl-3-(trifluoromethyl)phenyl)ureido]phenyl}-9H-purin-6-yl)-methyl-carbamic acid tert-butyl ester was dissolved, and 15 μL of acetic acid and 20 mg (0.20 mmol) of 1-methylpiperazine were added thereto, and the mixture solution was stirred at room temperature for 30 minutes. To the reaction solution, 10 mg (0.26 mmol) of sodium cyanoborohydride was further added and the resulting solution was stirred at room temperature for one hour. The reaction solution was concentrated and partitioned between water and ethyl acetate and the organic layer was washed with a saturated sodium chloride solution, concentrated under reduced pressure and purified by a silica gel column (ethyl acetate:methanol=4:1). The obtained intermediate was dissolved in 1 mL of trifluoroacetic acid and stirred for one hour. The reaction solution was concentrated and partitioned between a saturated sodium bicarbonate solution and ethyl acetate, and the organic layer was washed with a saturated sodium chloride solution, concentrated under reduced pressure, and purified by trituration with ethyl acetate to obtain 27.4 mg (70%) of a target product as a white solid.

Workup

  1. stirringthe resulting solution was stirred at room temperature for one hour
  2. concentrationThe reaction solution was concentrated
  3. custompartitioned between water and ethyl acetate
  4. washthe organic layer was washed with a saturated sodium chloride solution
  5. concentrationconcentrated under reduced pressure
  6. custompurified by a silica gel column (ethyl acetate:methanol=4:1)
  7. dissolutionThe obtained intermediate was dissolved in 1 mL of trifluoroacetic acid
  8. stirringstirred for one hour
  9. concentrationThe reaction solution was concentrated
  10. custompartitioned between a saturated sodium bicarbonate solution and ethyl acetate
  11. washthe organic layer was washed with a saturated sodium chloride solution
  12. concentrationconcentrated under reduced pressure
  13. custompurified by trituration with ethyl acetate

Sources & evidence

ORD record
ord-412cf2f8d1274b77ba564af14b84cd3a
Source dataset
uspto-grants-2013_12
Patent number
US08609656B2

Reaction notes

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