2,6-Lutidine → HCID 86597460, compound

HRID 2112611Notes

Reaction equation

HRID 2112611 reaction equation
[CH:1]1([C:8]2[C:13]([C:14]3[C:32]([F:33])=[CH:31][C:17]([O:18][CH2:19][CH2:20][CH2:21][N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:16][C:15]=3[F:34])=[C:12](O)[N:11]=[C:10]([C:36]3[CH:41]=[N:40][CH:39]=[CH:38][N:37]=3)[N:9]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.P(Cl)(Cl)([Cl:44])=O.N1C(C)=CC=CC=1C>>[Cl:44][C:12]1[N:11]=[C:10]([C:36]2[CH:41]=[N:40][CH:39]=[CH:38][N:37]=2)[N:9]=[C:8]([CH:1]2[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[C:13]=1[C:14]1[C:32]([F:33])=[CH:31][C:17]([O:18][CH2:19][CH2:20][CH2:21][N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:16][C:15]=1[F:34]

Participants

4

Reactant 3

HCID 79372,6-LutidineHCID 24813Phosphorus oxychlorideHCID 178483890HCID 178483890, compound

Product 1

HCID 86597460HCID 86597460, compound

Conditions

Temperature
110 °C

Procedure

To tert-butyl {3-[4-(4-cycloheptyl-6-hydroxy-2-pyrazin-2-ylpyrimidin-5-yl)-3,5-difluorophenoxy]propyl}methylcarbamate (130 mg, 0.23 mmol) is added 2.0 mL of phosphorous oxychloride and 1.0 mL of 2,6-lutidine, and the mixture is heated at 110° C. for 12 h. The excess phosphorous oxychloride is removed in vaccuo, and the resulting residue is chromatographed over silica gel, eluting with 30% ethyl acetate in hexanes. Concentration provides tert-butyl {3-[4-(6-chloro-4-cycloheptyl-2-pyrazin-2-ylpyrimidin-5-yl)-3,5-difluorophenoxy]propyl}methylcarbamate as a light yellow semi-solid (23 mg). MS: m/z 588.0 (M+H). This product is dissolved in 2 mL of methylene chloride, and 2.3 mL of trifluoroacetic acid is added. The mixture is stirred at 40° C. for 20 h, and concentrated in vaccuo, yielding N-{3-[4-(4-chloro-6-cycloheptyl-2-pyrazin-2-ylpyrimidin-5-yl)-3,5-difluorophenoxy]propyl}-N-methylamine as a trifluoroacetic acid salt as a light yellow semi-solid (24 mg). MS: m/z 488.2 (M+H).

Workup

  1. customThe excess phosphorous oxychloride is removed in vaccuo
  2. customthe resulting residue is chromatographed over silica gel
  3. washeluting with 30% ethyl acetate in hexanes
  4. concentrationConcentration

Sources & evidence

ORD record
ord-6ffffdefc45f42a596e905c78591c218
Source dataset
uspto-grants-2009_04
Patent number
US07524849B2

Reaction notes

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