Water → HCID 71738048, compound

HRID 338779Notes

Reaction equation

HRID 338779 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=3)[C:15](O)=[O:16])[CH2:9][CH2:8][C:6]=2[N:7]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[F:33][C:34]1[CH:40]=[CH:39][C:37]([NH2:38])=[CH:36][C:35]=1[C:41]([F:44])([F:43])[F:42].O>CS(C)=O.[Cl-].[Na+].O>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=3)[C:15]([NH:38][C:37]3[CH:39]=[CH:40][C:34]([F:33])=[C:35]([C:41]([F:44])([F:42])[F:43])[CH:36]=3)=[O:16])[CH2:9][CH2:8][C:6]=2[N:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 753774-Fluoro-3-(trifluoromethyl)aniline2×HCID 866958153-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzoic acid

Product 1

HCID 71738048HCID 71738048, compoundYield 9.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzoic acid (54 mg, 0.20 mmol) and 1,1′-Carbonyldiimidazole (36 mg, 0.22 mmol) in 3.0 mL DMSO was stirred at rt for 5 minutes, and then heated at 60° C. for 25 minutes. Then 4-fluoro-3-(trifluoromethyl)aniline (0.051 mL, 0.40 mmol) was added, and the reaction heated at 80° C. for 46 hours. Next, an additional 2 small drops of 4-fluoro-3-(trifluoromethyl)aniline was added and the reaction heated at 160° C. for 1.5 hours. Upon cooling to rt, the reaction mixture was added to a solution of 35 mL H2O plus 5 mL brine, and the resulting precipitate filtered and rinsed with H2O and hexane/EtOAc. The precipitate was chromatographed using CHCl3/MeOH, and the resulting solid chromatographed again using EtOAc/MeOH to give the title compound as a yellow solid (8 mg, 9%). 1H NMR (Acetone-d6) δ: 9.77 (br. s., 1H), 8.31 (dd, J=6.4, 2.6 Hz, 1H), 8.10-8.17 (m, 2H), 7.62-7.64 (m, 1H), 7.35-7.44 (m, 3H), 7.24-7.28 (m, 1H), 5.79 (br. s., 2H), 4.35 (s, 2H), 3.70 (t, J=5.9 Hz, 2H), 2.80-2.86 (m, 2H).

Workup

  1. temperatureheated at 60° C. for 25 minutes
  2. temperaturethe reaction heated at 80° C. for 46 hours
  3. temperaturethe reaction heated at 160° C. for 1.5 hours
  4. temperatureUpon cooling to rt
  5. filtrationthe resulting precipitate filtered
  6. washrinsed with H2O and hexane/EtOAc
  7. customThe precipitate was chromatographed
  8. customthe resulting solid chromatographed again using EtOAc/MeOH

Sources & evidence

ORD record
ord-f52117e023ed475d983991c1f68f207f
Source dataset
uspto-grants-2014_11
Patent number
US08889870B2

Reaction notes

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