Potassium Carbonate → 4-(3-chloro-4-fluorophenyl)-6-((S)-4-(3-chloropyridin-2-yl)-2-methylpiperazin-1-yl)-2-((S)-2-methylpyrrolidin-1-yl)pyrimidine

HRID 230971Notes

Reaction equation

HRID 230971 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[C:10]([Cl:15])[CH:9]=2)[CH:5]=[C:4]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][N:23]=3)[CH2:18][C@@H:17]2[CH3:29])[N:3]=1.Br.[CH3:31][C@H:32]1[CH2:36][CH2:35][CH2:34][NH:33]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[Cl:15][C:10]1[CH:9]=[C:8]([C:6]2[CH:5]=[C:4]([N:16]3[CH2:21][CH2:20][N:19]([C:22]4[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][N:23]=4)[CH2:18][C@@H:17]3[CH3:29])[N:3]=[C:2]([N:33]3[CH2:34][CH2:35][CH2:36][C@@H:32]3[CH3:31])[N:7]=2)[CH:13]=[CH:12][C:11]=1[F:14]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 20779371(S)-2-methylpyrrolidine hydrobromideHCID 577618042-chloro-4-(3-chloro-4-fluorophenyl)-6-((S)-4-(3-chloropyridin-2-yl)-2-methylpiperazin-1-yl)pyrimidine

Product 1

HCID 577615814-(3-chloro-4-fluorophenyl)-6-((S)-4-(3-chloropyridin-2-yl)-2-methylpiperazin-1-yl)-2-((S)-2-methylpyrrolidin-1-yl)pyrimidine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Dissolve 2-chloro-4-(3-chloro-4-fluorophenyl)-6-((S)-4-(3-chloropyridin-2-yl)-2-methylpiperazin-1-yl)pyrimidine (45 mg, 0.1 mmol) and (S)-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. Purify by flash column chromatography using 10-20% EtOAc/hexane to afford the title product as viscous oil. NMR (CDCl3) δ1.31 (3H, d, J=2.1), 1.41(3H, d, J=2.3), 1.62 (2H, m), 1.93 (3H, m), 3.00 (2H, m), 3.35 (1H, t), 3.65 (2H, m), 3.81(2H, m), 4.35 (1H, m), 4.68 (1H, bs), 6.22 (1H, s), 6.87 (1H, m), 7.16 (1H, t), 7.61 (1H, m), 7.88 (1H, m), 8.06 (1H, m), 8.20 (1H, m). Mass spec m/z=501.22.

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-8f50c6502da849fb9f4306e4b0c607c0
Source dataset
uspto-grants-2009_07
Patent number
US07566712B2

Reaction notes

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