Trifluoroacetic acid → HCID 73386767, compound

HRID 1480767Notes

Reaction equation

HRID 1480767 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:13][CH:12]([O:14][CH3:15])[CH2:11]2)=[O:9])=[CH:4][C:3]=1[O:16][CH3:17].C(O)(C(F)(F)F)=O.[CH3:25][N:26]1[CH:30]=[C:29]([C:31]2[C:36]3[N:37]=[C:38](S(C)(=O)=O)[N:39]=[CH:40][C:35]=3[CH:34]=[CH:33][N:32]=2)[CH:28]=[N:27]1>FC(F)(F)CO.CCOC(C)=O>[CH3:17][O:16][C:3]1[CH:4]=[C:5]([C:8]([N:10]2[CH2:13][CH:12]([O:14][CH3:15])[CH2:11]2)=[O:9])[CH:6]=[CH:7][C:2]=1[NH:1][C:38]1[N:39]=[CH:40][C:35]2[CH:34]=[CH:33][N:32]=[C:31]([C:29]3[CH:28]=[N:27][N:26]([CH3:25])[CH:30]=3)[C:36]=2[N:37]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 68310218HCID 68310218, compoundHCID 89996010HCID 89996010, compound

Product 1

HCID 73386767HCID 73386767, compoundYield 20.4%

Reagents, catalysts & solvents 2

HCID 64092,2,2-TrifluoroethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (4-amino-3-methoxyphenyl)(3-methoxyazetidin-1-yl)methanone (Preparation 28, 56 mg, 0.237 mmol), TFA (46 μL, 0.601 mmol) and 8-(1-methyl-1H-pyrazol-4-yl)-2-(methylsulfonyl)pyrido[3,4-d]pyrimidine (Preparation 35, 35 mg, 0.121 mmol) in 2,2,2-trifluoroethanol (0.6 mL) was heated to reflux for 5 hours and then to 80° C. for 18 hours. The reaction was diluted with EtOAc, quenched with aqueous saturated NaHCO3 and the aqueous layer extracted with EtOAc. The combined organic layers were washed with water, brine, dried, concentrated in vacuo and purified by silica gel column chromatography eluting with 0 to 100% EtOAc in cyclohexane followed by a second chromatography eluting with 0 to 10% MeOH in EtOAc to afford the title compound (11 mg, 20%). 1H 1HNMR (500 MHz, DMSO-d6): δ 9.43 (s, 1H), 9.17 (s, 1H), 8.64 (s, 1H), 8.40 (d, J=5.2 Hz, 1H), 8.28 (s, 1H), 8.05 (d, J=8.1 Hz, 1H), 7.62 (d, J=5.2 Hz, 1H), 7.42-7.28 (m, 2H), 4.56 (s, 1H), 4.33-4.20 (m, 3H), 3.89-3.87 (m, 7H), 3.25 (s, 3H).

Workup

  1. temperatureto reflux for 5 hours
  2. customquenched with aqueous saturated NaHCO3
  3. extractionthe aqueous layer extracted with EtOAc
  4. washThe combined organic layers were washed with water, brine
  5. customdried
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel column chromatography
  8. washeluting with 0 to 100% EtOAc in cyclohexane
  9. washeluting with 0 to 10% MeOH in EtOAc

Sources & evidence

ORD record
ord-d74aff362a44465db511a47edd64f5f2
Source dataset
uspto-grants-2016_08
Patent number
US09409907B2

Reaction notes

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