Acetic Acid → HCID 68780522, compound

HRID 2264515Notes

Reaction equation

HRID 2264515 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]([NH:9][CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[N:6]=[C:5]([NH:16][CH2:17][CH2:18][OH:19])[N:4]=1.[CH2:20]([O:22][C:23]1[CH:24]=[C:25]([CH:28]=[C:29]([O:32][CH2:33][CH3:34])[C:30]=1[F:31])[CH:26]=O)[CH3:21].C(N(C(C)C)C(C)C)C.C(O)(=O)C.C([BH3-])#N.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.O>[CH2:20]([O:22][C:23]1[CH:24]=[C:25]([CH:28]=[C:29]([O:32][CH2:33][CH3:34])[C:30]=1[F:31])[CH2:26][N:13]1[CH2:12][CH2:11][CH:10]([NH:9][C:7]2[N:8]=[C:3]([O:2][CH3:1])[N:4]=[C:5]([NH:16][CH2:17][CH2:18][OH:19])[N:6]=2)[CH2:15][CH2:14]1)[CH3:21]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 58972439HCID 58972439, compoundHCID 591282733,5-Diethoxy-4-fluoro-benzaldehyde

Product 1

HCID 68780522HCID 68780522, compoundYield 45.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-[4-methoxy-6-(piperidin-4-ylamino)-[1,3,5]triazin-2-ylamino]-ethanol (0.19 g, 0.71 mmol, 1.0 equiv; intermediate C26) and 3,5-diethoxy-4-fluoro-benzaldehyde (0.17 g, 0.78 mmol, 1.1 equiv; intermediate D12) in ethanol (10 mL) under an atmosphere of Ar was added N-ethyl diisopropylamine (0.28 mL, 0.21 g, 1.63 mmol, 2.29 equiv) and glacial acetic acid (0.10 mL, 0.10 g, 1.67 mmol, 2.35 equiv) and the mixture heated to 50° C. for 2 h. After cooling down to 30° C., sodium cyanoborohydride (0.12 g, 1.91 mmol, 2.7 equiv) was added and the reaction mixture heated again to 50° C. for 1.5 h. It was then poured into crashed ice, the pH of the water phase adjusted to ˜10 by addition of a sat. solution of sodium carbonate and the mixture extracted three times with dichloromethane. The combined organic phases were washed with water, dried over MgSO4, filtered and concentrated by evaporation under reduced pressure. The crude product was purified by column chromatography on silica eluting with a gradient of dichloromethane/methanol to give 0.15 g (45%) of the title compound as light yellow oil. MS (ISP): 465.2 [M+H]+.

Workup

  1. temperatureAfter cooling down to 30° C.
  2. temperaturethe reaction mixture heated again to 50° C. for 1.5 h
  3. additionIt was then poured
  4. extractionthe mixture extracted three times with dichloromethane
  5. washThe combined organic phases were washed with water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated by evaporation under reduced pressure
  9. customThe crude product was purified by column chromatography on silica eluting with a gradient of dichloromethane/methanol

Sources & evidence

ORD record
ord-8c023bf4b9be4c33b6a04514f76a39c5
Source dataset
uspto-grants-2010_12
Patent number
US07855194B2

Reaction notes

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