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 510238ノート

反応式

HRID 510238 の反応式
[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]

参加物

8

反応物 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

生成物 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)methanone収率 67.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-dc668e7651ec420f9b27e813c42f2bb8
出典データセット
uspto-grants-2015_08
特許番号
US09096596B2

反応ノート

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