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 2272716Notes

Reaction equation

HRID 2272716 reaction equation
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]

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-c91ca83700704f8fa47afe074f0c06b8
Source dataset
uspto-grants-2015_09
Patent number
US09120778B2

Reaction notes

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