m-Chloroperbenzoic acid → HCID 59553290, compound

HRID 1171379Notes

Reaction equation

HRID 1171379 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:27]=[C:28]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[CH:29]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21](SC)[N:20]=2)=[CH:10][CH:9]=1)=[O:6].C1C=C(Cl)C=C(C(OO)=O)C=1.[CH3:47][N:48]([CH3:55])[CH2:49][C:50]([CH3:54])([CH3:53])[CH2:51][NH2:52]>C(Cl)(Cl)Cl.CS(C)=O.C(Cl)Cl>[CH3:47][N:48]([CH3:55])[CH2:49][C:50]([CH3:54])([CH3:53])[CH2:51][NH:52][C:21]1[N:20]=[C:19]([O:18][C:11]2[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:8]([NH:7][C:5](=[O:6])[C:4]3[CH:27]=[C:28]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)[CH:29]=[C:2]([F:1])[CH:3]=3)=[CH:9][CH:10]=2)[CH:24]=[CH:23][N:22]=1

Participants

7

Reactant 3

HCID 70297m-Chloroperbenzoic acidHCID 104477N,N,2,2-Tetramethylpropane-1,3-diamineHCID 595530703-fluoro-N-(4-{[2-(methylthio)pyrimidin-4-yl]oxy}-1-naphthyl)-5-morpholin-4-ylbenzamide

Product 1

HCID 59553290HCID 59553290, compoundYield 11.5%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 6212ChloroformSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
85 °C

Procedure

3-Fluoro-N-[4-(2-methylsulfanyl-pyrimidin-4-yloxy)-naphthalen-1-yl]-5-morpholin-4-yl-benzamide (457 mg, 0.908 mmol) and MCPBA (447 mg, 1.998 mmol) in CHCl3 (5 ml) is stirred at room temperature for 1 h. The mixture is diluted with CHCl3 (5 ml) washed with sat'd NaHCO3 solution (5 ml), water (5 ml), dried over Na2SO4 and concentrated to give a yellow solid. The yellow solid is mixed with N,N,2,2-tetramethyl-1,3-propanediamine (1.18 g, 9.08 mmol) and DIPA (1.58 ml, 9.08 mmol) in DMSO (2 ml), and heated to 85° C. for 4 h. The resulting mixture is diluted with CH2Cl2 (2 ml), washed with 0.01 N NaOH, dried over Na2SO4, concentrated. The residue is purified by column chromatography on silica gel (EtOAc) to give N-{4-[2-(3-dimethylamino-2,2-dimethyl-propylamino)-pyrimidin-4-yloxy]-naphthalen-1-yl}-3-fluoro-5-morpholin-4-yl-benzamide as a white solid (60 mg). 1H NMR (400 MHz, CDCl3) δ 8.19 (s, 1H), 8.08 (s, 1H), 8.01 (d, 1H), 7.92 (m, 2H), 7.57 (t, H), 7.51 (t, 1H), 7.30 (d, 2H), 7.21 (d, 1H), 6.82 (dt, 1H), 5.87 (s, 1H), 4.33 (m, 1H), 3.23 (s, 1H), 2.27 (s, 6H), 2.21 (m, 2H), 2.02 (m, 2H), 1.82 (m, 2H), 1.57 (m, 3H), 1.39 (m, 3H), 0.98 (s, 6H); MS 586.37 (M+1).

Workup

  1. washwashed with sat'd NaHCO3 solution (5 ml), water (5 ml)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customto give a yellow solid
  5. washwashed with 0.01 N NaOH
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue is purified by column chromatography on silica gel (EtOAc)

Sources & evidence

ORD record
ord-e3cafb4125704fd8b09ae8349cf721e6
Source dataset
uspto-grants-2010_11
Patent number
US07829560B2

Reaction notes

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