Methyl iodide → HCID 57761357, compound

HRID 230956Notes

Reaction equation

HRID 230956 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]=[C:13]([N:15]3[CH2:19][CH2:18][CH2:17][CH:16]3[CH3:20])[N:12]=[C:11]([N:21]3[CH2:26][CH2:25][N:24]([C:27]4[N:32]=[CH:31][C:30]([OH:33])=[CH:29][C:28]=4[CH3:34])[CH2:23][CH2:22]3)[CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].[H-].[Na+].[CH3:37]I>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[C:11]([N:21]3[CH2:22][CH2:23][N:24]([C:27]4[C:28]([CH3:34])=[CH:29][C:30]([O:33][CH3:37])=[CH:31][N:32]=4)[CH2:25][CH2:26]3)[N:12]=[C:13]([N:15]3[CH2:19][CH2:18][CH2:17][CH:16]3[CH3:20])[N:14]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 57761731HCID 57761731, compound

Product 1

HCID 57761357HCID 57761357, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-{4-[6-(3-chloro-4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-piperazin-1-yl}-5-methyl-pyridin-3-ol (50 mg, 0.10 mmol) in DMF add 60% NaH (12 mg, 0.30 mmol). Stir the solution at room temperature for 30 minutes. Add methyl iodide (0.3 mmol) and stir the solution at room temperature for 2 hours. Partition between EtOAc and water. Wash with brine, dry the solution (Na2SO4), and concentrate under reduced pressure. Purify the residue by flash column chromatography eluting with EtOAc:Hexanes (1:4) to afford 4-(3-chloro-4-fluoro-phenyl)-6-[4-(5-methoxy-3-methyl-pyridin-2-yl)-piperazin-1-yl]-2-(2-methyl-pyrrolidin-1-yl)-pyrimidine as a solid. 1H NMR (300 MHz, CDCl3): δ1.30 (t, 3H, J=6.3 Hz, CH3); 1.70 (m, 1H, CH2CH2); 1.91 (m, 1H, CH2CH2); 2.06 (m, 2H, CH2CH2); 2.33 (s, 3H, Ar—CH3); 3.13 (m, 4H); 3.67 (m, 2H); 3.78 (m, 4H); 3.80 (s, OCH3); 4.33 (m, 1H); 6.25 (s, 1H, Ar—H); 7.06 (d, J=2.4 Hz, 1H); 7.18 (m, 1H); 7.88 (m, 2 H); 7.86 (m, 1H); 8.07 (m, 1H).

Workup

  1. customPartition between EtOAc and water
  2. washWash with brine
  3. dry with materialdry the solution (Na2SO4)
  4. concentrationconcentrate under reduced pressure
  5. customPurify the residue by flash column chromatography
  6. washeluting with EtOAc:Hexanes (1:4)

Sources & evidence

ORD record
ord-beacea1ab00d4cbf871819aad5293de0
Source dataset
uspto-grants-2009_07
Patent number
US07566712B2

Reaction notes

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