1,4-Dioxane → HCID 90452625, compound

HRID 2272723Notes

Reaction equation

HRID 2272723 reaction equation
CC1(C)[O:6][C@@H:5]([CH2:7][N:8]2[CH:13]=[C:12]([C:14]([OH:16])=O)[C:11](=[O:17])[N:10]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:9]2=[O:25])[CH2:4][O:3]1.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[CH3:60][O:61][C:62]1[CH:63]=[C:64]2[C:69](=[CH:70][C:71]=1[O:72][CH3:73])[N:68]=[CH:67][CH:66]=[C:65]2[O:74][C:75]1[CH:80]=[CH:79][C:78]([NH2:81])=[CH:77][C:76]=1[F:82].O1CCOCC1>CN(C)C=O.CCOC(C)=O.Cl>[CH3:60][O:61][C:62]1[CH:63]=[C:64]2[C:69](=[CH:70][C:71]=1[O:72][CH3:73])[N:68]=[CH:67][CH:66]=[C:65]2[O:74][C:75]1[CH:80]=[CH:79][C:78]([NH:81][C:14]([C:12]2[C:11](=[O:17])[N:10]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:9](=[O:25])[N:8]([CH2:7][C@H:5]([OH:6])[CH2:4][OH:3])[CH:13]=2)=[O:16])=[CH:77][C:76]=1[F:82]

Participants

9

Reactant 5

HCID 312751,4-DioxaneHCID 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 89582840HCID 89582840, compound

Product 1

HCID 90452625HCID 90452625, compound

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-((S)-2,2-Dimethyl-1,3-dioxolan-4-ylmethyl)-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (0.0446 g, 0.122 mmol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.0466 g, 0.122 mmol) in N,N-dimethylformamide (2.00 mL) was added N,N-diisopropylethylamine (0.0388 mL, 0.223 mmol) and stirred at rt for 15 min. 4-(6,7-Dimethoxyquinolin-4-yloxy)-3-fluorophenylamine (0.035 g, 0.11 mmol) was added and stirred overnight. The solution was diluted with EtOAc, washed with 1N Na2CO3, water and brine then dried over MgSO4 and concentrated. MeOH was added (1 mL) and a solid separated. This material was dissolved in 4 M of hydrogen chloride in 1,4-dioxane (2 mL, 8 mmol), stirred for 2 h and then concentrated. To this product was added MeOH and the precipitate collected to give a white solid. mp=165-6° C.; LCMS m/z=621 (M+1); 1H NMR (DMSO) δ: 11.0 (s, 1H), 8.72 (s, 1H), 8.48 9d, 1H, J=5.4 Hz), 8.01, 7.98 (dd, 1H, J=2.4, 13.5 Hz), 7.52-7.55 (j, 1H), 7.34-7.46 (m, 6H), 6.47 (d, 1H, J=5.4 Hz), 6.17 (d, 1H, J=5 Hz), 4.78 (t, 1H, J=5.7 Hz), 4.22 (d, 1H, J=10 Hz), 3.94 (d, 6H), 3.75-3.78 (m, 2H), 3.3 (m, 2H).

Workup

  1. stirringstirred overnight
  2. washwashed with 1N Na2CO3, water and brine
  3. dry with materialthen dried over MgSO4
  4. concentrationconcentrated
  5. additionMeOH was added (1 mL)
  6. customa solid separated
  7. stirringstirred for 2 h
  8. concentrationconcentrated
  9. additionTo this product was added MeOH
  10. customthe precipitate collected
  11. customto give a white solid

Sources & evidence

ORD record
ord-76378f25334a48d6986366005b34454f
Source dataset
uspto-grants-2015_09
Patent number
US09120778B2

Reaction notes

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