Diisopropylethylamine → 1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylicacid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]amide

HRID 573412ノート

反応式

HRID 573412 の反応式
F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.[CH2:25]([N:27]1[CH:32]=[C:31]([C:33]([OH:35])=O)[C:30](=[O:36])[N:29]([C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=2)[C:28]1=[O:44])[CH3:26].C(N(CC)C(C)C)(C)C.[CH3:54][O:55][C:56]1[CH:57]=[C:58]2[C:63](=[CH:64][C:65]=1[O:66][CH3:67])[N:62]=[CH:61][CH:60]=[C:59]2[O:68][C:69]1[CH:74]=[CH:73][C:72]([NH2:75])=[CH:71][C:70]=1[F:76]>CN(C)C=O.CCOC(C)=O>[CH3:54][O:55][C:56]1[CH:57]=[C:58]2[C:63](=[CH:64][C:65]=1[O:66][CH3:67])[N:62]=[CH:61][CH:60]=[C:59]2[O:68][C:69]1[CH:74]=[CH:73][C:72]([NH:75][C:33]([C:31]2[C:30](=[O:36])[N:29]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)[C:28](=[O:44])[N:27]([CH2:25][CH3:26])[CH:32]=2)=[O:35])=[CH:71][C:70]=1[F:76]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 114269974-((6,7-Dimethoxyquinolin-4-yl)oxy)-3-fluorobenzenamineHCID 895826181-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid

生成物 1

HCID 715567591-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylicacid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]amide

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (HATU) (0.072 g, 0.19 mmol) and 1-ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (0.053 g, 0.19 mmol) in N,N-dimethylformamide (2 mL) was added N,N-diisopropylethylamine (0.055 mL, 0.32 mmol). After 15 min stirring at rt, 4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenylamine (0.05 g, 0.2 mmol) was added. The reaction was stirred at rt for 12 h, diluted with EtOAc (25 mL), then washed with 1N Na2CO3, water and brine and then dried over MgSO4. The product was crystallized from MeOH to give 75 mg (68%) as a white solid. mp=151-4° C.; LCMS m/z=575 (M+1); 1H NMR (DMSO) δ: 11.04 (s, 1H), 8.89 (s, 1H), 8.47 (d, 1H, J=5.4 Hz), 7.98, 8.01 (dd, 1H, J=2.3, 12.6 Hz), 7.52-7.56 (m, 2H), 7.33-7.46 (m, 6H), 6.47 (d, 1H, J=5.4 Hz), 4.01 (q, 2H, J=7 Hz), 3.98 (d, 6H), 13.0 (t, 3H, J=7 Hz).

後処理

  1. stirringThe reaction was stirred at rt for 12 h
  2. washwashed with 1N Na2CO3, water and brine
  3. dry with materialdried over MgSO4
  4. customThe product was crystallized from MeOH
  5. customto give 75 mg (68%) as a white solid

出典と根拠

ORDレコード
ord-71c0a35dc06c47069a21709ecf27f2c4
出典データセット
uspto-grants-2015_05
特許番号
US09029538B2

反応ノート

読み込み中…