3-(Trifluoromethyl)benzoic acid → N-(4-Methyl-3-{2-[4-(4-methyl-piperazine-1-carbonyl)-phenylamino]-5-oxo-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl}-phenyl)-3-trifluoromethylbenzamide

HRID 1853957

反応式

HRID 1853957 の反応式
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:35])=[C:6]([N:8]2[CH2:33][CH2:32][C:11]3[N:12]=[C:13]([NH:16][C:17]4[CH:22]=[CH:21][C:20]([C:23]([N:25]5[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]5)=[O:24])=[CH:19][CH:18]=4)[N:14]=[CH:15][C:10]=3[C:9]2=[O:34])[CH:7]=1.[F:36][C:37]([F:48])([F:47])[C:38]1[CH:39]=[C:40]([CH:44]=[CH:45][CH:46]=1)[C:41](O)=[O:42].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OC(=O)C)C>[CH3:35][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:41](=[O:42])[C:40]2[CH:44]=[CH:45][CH:46]=[C:38]([C:37]([F:36])([F:47])[F:48])[CH:39]=2)=[CH:7][C:6]=1[N:8]1[CH2:33][CH2:32][C:11]2[N:12]=[C:13]([NH:16][C:17]3[CH:18]=[CH:19][C:20]([C:23]([N:25]4[CH2:26][CH2:27][N:28]([CH3:31])[CH2:29][CH2:30]4)=[O:24])=[CH:21][CH:22]=3)[N:14]=[CH:15][C:10]=2[C:9]1=[O:34]

参加物

7

反応物 4

HCID 99633-(Trifluoromethyl)benzoic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 673290586-(5-Amino-2-methyl-phenyl)-2-[4-(4-methyl-piperazine-1-carbonyl)phenylamino]-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one

生成物 1

HCID 67329059N-(4-Methyl-3-{2-[4-(4-methyl-piperazine-1-carbonyl)-phenylamino]-5-oxo-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl}-phenyl)-3-trifluoromethylbenzamide収率 72.3%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 6-(5-Amino-2-methyl-phenyl)-2-[4-(4-methyl-piperazine-1-carbonyl)phenylamino]-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one (70.7 mg, 0.15 mmol), 3-Trifluoromethyl benzoic acid (28.5 mg, 0.15 mmol), and DIPEA (78 μl, 0.45 mmol) in DMF was added HATU (59 mg, 0.15 mmol), and the reaction mixture was stirred for 3 hour at room temperature. The reaction mixture was diluted with ethylacetate and washed with 5% aqueous sodium bisulphate solution, saturated aqueous sodium bicarbonate solution and brine. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. The crude product obtained was purified by column chromatography (SiO2, 2-10% methanol in chloroform) to give 69.8 mg (72.3%) of N-(4-Methyl-3-{2-[4-(4-methyl-piperazine-1-carbonyl)phenylamino]-5-oxo-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl}-phenyl)-3-trifluoromethyl-benzamide [24] as a pale yellow solid.

後処理

  1. washwashed with 5% aqueous sodium bisulphate solution, saturated aqueous sodium bicarbonate solution and brine
  2. dry with materialThe organic layer was dried over sodium sulphate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product obtained
  5. customwas purified by column chromatography (SiO2, 2-10% methanol in chloroform)

出典と根拠

ORDレコード
ord-934dd017718340abb1571d761ca53424
出典データセット
uspto-grants-2015_02
特許番号
US08962637B2

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