N,N-Diethylaniline → HCID 18456543, compound

HRID 1272377Notes

Reaction equation

HRID 1272377 reaction equation
[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14](O)=[N:13][C:12]([C:19]3[CH:20]=[N:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=3)=[N:11][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:31])=O.C(N(CC)C1C=CC=CC=1)C>>[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([Cl:31])=[N:13][C:12]([C:19]3[CH:20]=[N:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=3)=[N:11][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 7061N,N-DiethylanilineHCID 24813Phosphorus oxychlorideHCID 178517476HCID 178517476, compound

Product 1

HCID 18456543HCID 18456543, compound

Conditions

Temperature
110 °C

Procedure

A mixture of 232 mg (0.6 mmol) of 7-benzyl-2-[6-(trifluoromethyl)pyridin-3-yl]-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-ol from Step A and 1.0 mL of phosphorous oxychloride in a 25-mL round bottom flask was treated with 90 mg (0.095 mL, 0.6 mmol) of N,N-diethylaniline. The mixture was warmed to 110° C. After 4 h, it was cooled to ambient temperature and concentrated in vacuo. Water (15–20 mL) was added. The mixture was neutralized by the addition of solid sodium bicarbonate and extracted with 2 portions of ethyl acetate. The combined organic phases were washed with brine, dried, and concentrated. Purification by flash chromatography (silica gel, 0 to 20% ethyl acetate/hexane step gradient) gave 220 mg of a light yellow oil. LC-MS 405.2 (M+1).

Workup

  1. temperatureit was cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. additionWater (15–20 mL) was added
  4. additionThe mixture was neutralized by the addition of solid sodium bicarbonate
  5. extractionextracted with 2 portions of ethyl acetate
  6. washThe combined organic phases were washed with brine
  7. customdried
  8. concentrationconcentrated
  9. customPurification by flash chromatography (silica gel, 0 to 20% ethyl acetate/hexane step gradient)

Sources & evidence

ORD record
ord-88ea5042226544208be5a88ae37e9855
Source dataset
uspto-grants-2007_04
Patent number
US07208498B2

Reaction notes

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