Trifluoroacetic acid → (2-chloro-4-fluoro-3-(trifluoromethyl)phenyl)(8-methyl-4-(1H-pyrazol-5-yl)-5,6-dihydropyrido[3,4-d]pyrimidin-7(8H)-yl)methanone

HRID 510238Notes

Reaction equation

HRID 510238 reaction equation
[CH3:1][CH:2]1[C:7]2[N:8]=[CH:9][N:10]=[C:11]([C:12]3[N:16](C4CCCCO4)[N:15]=[CH:14][CH:13]=3)[C:6]=2[CH2:5][CH2:4][NH:3]1.[Cl:23][C:24]1[C:32]([C:33]([F:36])([F:35])[F:34])=[C:31]([F:37])[CH:30]=[CH:29][C:25]=1[C:26](O)=[O:27].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(O)(C(F)(F)F)=O.C([SiH](CC)CC)C>C(Cl)Cl>[Cl:23][C:24]1[C:32]([C:33]([F:35])([F:36])[F:34])=[C:31]([F:37])[CH:30]=[CH:29][C:25]=1[C:26]([N:3]1[CH2:4][CH2:5][C:6]2[C:11]([C:12]3[NH:16][N:15]=[CH:14][CH:13]=3)=[N:10][CH:9]=[N:8][C:7]=2[CH:2]1[CH3:1])=[O:27]

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 674606182-Chloro-4-fluoro-3-(trifluoromethyl)benzoic acidHCID 904082318-methyl-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine

Product 1

HCID 90407253(2-chloro-4-fluoro-3-(trifluoromethyl)phenyl)(8-methyl-4-(1H-pyrazol-5-yl)-5,6-dihydropyrido[3,4-d]pyrimidin-7(8H)-yl)methanoneYield 67.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the product of Example 112, step g (60 mg, 0.20 mmol) in DCM (2 mL) was added 2-chloro-4-fluoro-3-(trifluoromethyl)benzoic acid (49 mg, 0.20 mmol), followed by EDCI (116 mg, 0.607 mmol), HOBt (19 mg, 0.14 mmol) and TEA (2.0 mL, 0.607 mmol). The reaction was stirred at room temperature overnight. The crude mixture was treated directly with TFA (0.8 mL) and triethylsilane (81 L, 0.20 mmol) and stirred for 3 h. The solvents were removed in vacuo and the residue was azeotroped with toluene (1×). Chromatography on SiO2 eluted with EtOAc/Hex afforded the desired product (59 mg, 66%). MS (ESI) mass calcd. C19H14ClF4N5O, 439.1. m/z found 440.1 [M+H]+. 1H NMR (500 MHz, MeOD): 9.08-8.87 (m, 1H), 7.92-7.68 (m, 2H), 7.57-7.44 (m, 1H), 7.10-6.92 (m, 1H), 5.71-5.63 (m, 1H), 3.68-3.33 (m, 3H), 3.19-3.08 (m, 1H), 1.77-1.56 (m, 3H).

Workup

  1. stirringstirred for 3 h
  2. customThe solvents were removed in vacuo
  3. customthe residue was azeotroped with toluene (1×)
  4. washChromatography on SiO2 eluted with EtOAc/Hex

Sources & evidence

ORD record
ord-dc668e7651ec420f9b27e813c42f2bb8
Source dataset
uspto-grants-2015_08
Patent number
US09096596B2

Reaction notes

Loading…