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 230965Notes

Reaction equation

HRID 230965 reaction equation
[Cl:1][C:2]1[C:3]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[CH:21]=[C:20]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[N:19]=[C:18](Cl)[N:17]=3)[C@H:12]([CH3:30])[CH2:11]2)=[N:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.Br.[CH3:32][C@@H:33]1[CH2:37][CH2:36][CH2:35][NH:34]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[Cl:1][C:2]1[C:3]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[CH:21]=[C:20]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[N:19]=[C:18]([N:34]4[CH2:35][CH2:36][CH2:37][C@H:33]4[CH3:32])[N:17]=3)[C@H:12]([CH3:30])[CH2:11]2)=[N:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 12444175(2R)-2-methylpyrrolidine hydrobromideHCID 57761470HCID 57761470, compound

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 6342AcetonitrileSolvent

Procedure

Dissolve 5-chloro-4-((R)-4-(2-chloro-6-(4-fluorophenyl)pyrimidin-4-yl)-3-methylpiperazin-1-yl)-2-methoxypyrimidine (45 mg, 0.1 mmol) and (R)-2-methylpyrrolidine hydrobromide (0.2 mmol, prepared essentially as described by Nijhuis et. al. (1989) J. Org. Chem. 54:209-216) in CH3CN (2.0 mL) under nitrogen atmosphere. Add K2CO3 (55 mg, 0.4 mmol) and heat at 80° C. for 20 hours. Concentrate under vacuum, dilute with water (5.0 mL), extract with EtOAc (3×3 mL) and dry with MgSO4. Filter, and concentrate under vacuum to afford crude product and purify by flash column chromatography using 20% EtOAc/hexane to afford the title product as viscous oil. NMR (CDCl3) δ 1.3 (6H, m), 1.69 (1H, m), 1.91 (1H, m), 2.06 (2H, m), 3.21 (1H, m), 3.35 (2H, m), 3.63 (2H, m), 3.94 (3H, s), 4.28 (2H, m), 4.45 (2H, m), 4.64 (1H, bs), 6.19 (1H, s), 7.07 (2H, t), 7.97 (2H, m), 8.08 (1H, s). Mass spec m/z=498.17.

Workup

  1. customprepared essentially
  2. concentrationConcentrate under vacuum
  3. additiondilute with water (5.0 mL)
  4. extractionextract with EtOAc (3×3 mL)
  5. dry with materialdry with MgSO4
  6. filtrationFilter
  7. concentrationconcentrate under vacuum
  8. customto afford crude product
  9. custompurify by flash column chromatography

Sources & evidence

ORD record
ord-9484b3f6da4d4eb2bc49ee0021a3a0fe
Source dataset
uspto-grants-2009_07
Patent number
US07566712B2

Reaction notes

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