Potassium Carbonate → 5-chloro-4-((R)-4-(6-(4-fluorophenyl)-2-((R)-2-methylpyrrolidin-1-yl)pyrimidin-4-yl)-3-methylpiperazin-1-yl)-2-methoxypyrimidine

HRID 230966Notes

Reaction equation

HRID 230966 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[N:5]=[C:4]([N:15]2[C:19]([CH3:20])=[CH:18][CH:17]=[C:16]2C)[N:3]=1.[Cl:22][C:23]1[C:24]([N:29]2[CH2:34][CH2:33][NH:32][C@H:31]([CH3:35])[CH2:30]2)=[N:25][CH:26]=C[CH:28]=1.[C:36]([O-:39])([O-])=O.[K+].[K+].CC([N:45](C)C)=O>O>[Cl:22][C:23]1[C:24]([N:29]2[CH2:34][CH2:33][N:32]([C:2]3[CH:7]=[C:6]([C:8]4[CH:9]=[CH:10][C:11]([F:14])=[CH:12][CH:13]=4)[N:5]=[C:4]([N:15]4[CH2:16][CH2:17][CH2:18][C@H:19]4[CH3:20])[N:3]=3)[C@H:31]([CH3:35])[CH2:30]2)=[N:25][C:26]([O:39][CH3:36])=[N:45][CH:28]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 31374DimethylacetamideHCID 11658551(R)-1-(3-chloropyridin-2-yl)-3-methylpiperazineHCID 577619584-Chloro-6-(4-fluorophenyl)-2-(2,5-dimethyl-1h-pyrrol-1-yl)pyrimidine

Product 1

HCID 577610325-chloro-4-((R)-4-(6-(4-fluorophenyl)-2-((R)-2-methylpyrrolidin-1-yl)pyrimidin-4-yl)-3-methylpiperazin-1-yl)-2-methoxypyrimidine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Dissolve 4-chloro-6-(4-fluorophenyl)-2-(2,5-dimethyl-1H-pyrrol-1-yl)pyrimidine (60.4 mg, 0.2 mmoles) and (R)-1-(3-chloro-pyridin-2-yl)-3-methyl-piperazine (42.4 mg, 0.2 mmoles) in DMA (2.0 mL) under nitrogen atmosphere. Add anhydrous powdered K2CO3 (0.4 mmoles) to this mixture and heat at 130° C. for 24 hours. Cool, dilute with water (5 mL), extract with EtOAc (3×2 mL) and dry over MgSO4. Filter and concentrate under vacuum to afford crude product and purify by flash column chromatography using 10% EtOAc/hexane to afford the title product as white amorphous solid. NMR (CDCl3) δ 1.47 (3H, d, J=1.7), 2.45 (6H, s), 3.04 (2H, m), 3.45 (1H, t), 3.84 (2H, t), 4.35 (1H, m), 4.85 (1H, bs), 5.9 (1H, s), 6.77 (1H, s), 6.89 (1H, m), 7.14 (2H, t), 7.63 (1H, d, J=2.3), 8.06 (2H, m), 8.21 (1H, m). Mass spec m/z=477.11.

Workup

  1. temperatureCool
  2. extractionextract with EtOAc (3×2 mL)
  3. dry with materialdry over MgSO4
  4. filtrationFilter
  5. concentrationconcentrate under vacuum
  6. customto afford crude product
  7. custompurify by flash column chromatography

Sources & evidence

ORD record
ord-748c8b91557f4fb3b32c428ca5b0950f
Source dataset
uspto-grants-2009_07
Patent number
US07566712B2

Reaction notes

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