Triethylamine → HCID 59333676, compound

HRID 421429Notes

Reaction equation

HRID 421429 reaction equation
C(N(CC)CC)C.[CH3:8][C:9]1([CH3:42])[NH:14][CH2:13][CH2:12][N:11]([C:15]2[N:16]([CH2:37][C:38]([F:41])([F:40])[F:39])[C:17]3[C:22]([N:23]=2)=[C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[N:20]=[C:19]([C:30]2[CH:31]=[N:32][C:33]([NH2:36])=[N:34][CH:35]=2)[N:18]=3)[CH2:10]1.C([O:46][CH2:47][C:48](Cl)=[O:49])(=O)C.C[O-].[Na+].CO>C(Cl)Cl.CO.O1CCCC1.C(Cl)Cl.CO>[NH2:36][C:33]1[N:34]=[CH:35][C:30]([C:19]2[N:18]=[C:17]3[C:22]([N:23]=[C:15]([N:11]4[CH2:12][CH2:13][N:14]([C:47](=[O:46])[CH2:48][OH:49])[C:9]([CH3:42])([CH3:8])[CH2:10]4)[N:16]3[CH2:37][C:38]([F:41])([F:39])[F:40])=[C:21]([N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)[N:20]=2)=[CH:31][N:32]=1

Participants

8

Reactant 4

HCID 8471Triethylamine2×HCID 26297Acetoxyacetyl chloride2×HCID 23694274Sodium methanolate methanolHCID 593335975-[8-(3,3-Dimethylpiperazin-1-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine

Product 1

HCID 59333676HCID 59333676, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 21226129Dichloromethane methanolSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

Triethylamine (63.1 μl, 0.45 mmol) was added to a methylene chloride solution (3.0 ml) of 5-[8-(3,3-dimethylpiperazin-1-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine (101.3 mg, 0.21 mmol) at room temperature followed by the addition of acetoxyacetyl chloride (27.4 μl, 0.25 mmol) with ice cooling. The resulting mixture was stirred at room temperature for 1 hour followed by the addition of triethylamine (17.2 μl, 0.13 mmol) and acetoxyacetyl chloride (6.8 μl, 0.06 mmol) with ice cooling and the resulting mixture was further stirred at room temperature for 16 hours. The reaction mixture was poured into methylene chloride-methanol (10:1), washed with saturated aqueous sodium hydrogen carbonate solution, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, a 25% by weight sodium methoxide-methanol solution (94.1 μl, 0.41 mmol) was added to a methanol-tetrahydrofuran (3:1) mixture solution (8.0 ml) of the resulting residue, and the resulting mixture was stirred at room temperature for 17 hours. The reaction mixture was poured into methylene chloride and washed with water and the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (94.2 mg, 83%) as a pale yellow solid.

Workup

  1. stirringthe resulting mixture was further stirred at room temperature for 16 hours
  2. washwashed with saturated aqueous sodium hydrogen carbonate solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. stirringthe resulting mixture was stirred at room temperature for 17 hours
  7. washwashed with water
  8. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  9. filtrationAfter filtration
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customthe resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)

Sources & evidence

ORD record
ord-f293eeb110a245b0a6c19058be13d2d4
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Reaction notes

Loading…