N,N-Diethylaniline → HCID 86597652, compound

HRID 1786309Notes

Reaction equation

HRID 1786309 reaction equation
[CH:1]1([C:8]2[N:13]3[N:14]=[CH:15][N:16]=[C:12]3[N:11]=[C:10](O)[C:9]=2[C:18]2[C:36]([F:37])=[CH:35][C:21]([O:22][CH2:23][CH2:24][CH2:25][N:26]([CH3:34])[C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:20][C:19]=2[F:38])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.P(Cl)(Cl)([Cl:41])=O.C(N(CC)C1C=CC=CC=1)C>>[Cl:41][C:10]1[C:9]([C:18]2[C:19]([F:38])=[CH:20][C:21]([O:22][CH2:23][CH2:24][CH2:25][N:26]([CH3:34])[C:27](=[O:33])[O:28][C:29]([CH3:30])([CH3:32])[CH3:31])=[CH:35][C:36]=2[F:37])=[C:8]([CH:1]2[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[N:13]2[N:14]=[CH:15][N:16]=[C:12]2[N:11]=1

Participants

4

Reactant 3

HCID 7061N,N-DiethylanilineHCID 24813Phosphorus oxychlorideHCID 178483889HCID 178483889, compound

Product 1

HCID 86597652HCID 86597652, compound

Conditions

Temperature
90 °C

Procedure

To tert-butyl 3-[4-(7-cycloheptyl-5-hydroxy[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-3,5-difluorophenoxy]propyl(methyl)carbamate (876 mg, 1.64 mmol) is added 5.8 mL of phosphorous oxychloride and 2.9 mL of N,N-diethylaniline, and the mixture is heated at 90° C. for 3 h. The excess phosphorous oxychloride is removed in vaccuo, and the resulting residue is diluted with ethyl acetate. The organic layer is washed with ice water and saturated sodium chloride (x2), dried over magnesium sulfate, and concentrated to a residue. The residue is chromatographed over silica gel, eluting with a gradient of hexanes to 40% ethyl acetate in hexanes. Concentration provides tert-butyl 3-[4-(5-chloro-7-cycloheptyl [1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-3,5-difluorophenoxy]propyl(methyl)carbamate as a light yellow oil (452 mg). MS: m/z 550.1 (M+H).

Workup

  1. customThe excess phosphorous oxychloride is removed in vaccuo
  2. additionthe resulting residue is diluted with ethyl acetate
  3. washThe organic layer is washed with ice water and saturated sodium chloride (x2)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated to a residue
  6. customThe residue is chromatographed over silica gel
  7. washeluting with a gradient of hexanes to 40% ethyl acetate in hexanes
  8. concentrationConcentration

Sources & evidence

ORD record
ord-ba1810bfcb95419989b90d1ac1d93088
Source dataset
uspto-grants-2009_03
Patent number
US07507739B2

Reaction notes

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