Dichloromethane → HCID 44623962, compound

HRID 2273989Notes

Reaction equation

HRID 2273989 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31]2[CH:39]=[CH:38][CH:37]=[CH:36][C:32]=2[C:33](O)=[O:34])=[CH:26][CH:25]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(Cl)Cl.C(N(C(C)C)C(C)C)C>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:17]=[CH:18][C:19]([NH:22][C:33](=[O:34])[C:32]2[CH:36]=[CH:37][CH:38]=[CH:39][C:31]=2[NH:30][C:27]2[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=2)=[CH:20][CH:21]=1

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 120159Anthranilic acid, N-(p-fluorophenyl)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 115945434-[(6,7-Dimethoxyquinolin-4-yl)oxy]aniline

Product 1

HCID 44623962HCID 44623962, compound

Procedure

4-(6,7-Dimethoxyquinolin-4-yloxy)benzenamine (60 mg, 202 μmol), 2-(4-fluorophenylamino)benzoic acid (56 mg, 243 μmol), and HATU (108 mg, 283 μmol) were combined in a resealable tube. DCM (1012 μl, 202 μmol) and N-ethyl-N-isopropylpropan-2-amine (71 μl, 405 μmol) were added, and the reaction mixture in the tube was allowed to stir at RT. Upon completion (as judged by LCMS), the reaction mixture was concentrated in vacuo, dissolved in minimal DMSO and purified by preparative HPLC {15-85% (0.1% TFA in CH3CN) in H2O over 20 min}. Fractions containing pure product were combined and neutralized with saturated aqueous NaHCO3 then extracted with EtOAc, dried over MgSO4, filtered, and concentrated in vacuo to afford pure N-(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-2-(4-fluorophenylamino)benzamide as a off-white solid. MS Calcd for C30H24FN3O4: [M]+=509. Found: [M+H]+=510.

Workup

  1. concentrationUpon completion (as judged by LCMS), the reaction mixture was concentrated in vacuo
  2. dissolutiondissolved in minimal DMSO
  3. custompurified by preparative HPLC {15-85% (0.1% TFA in CH3CN) in H2O over 20 min}
  4. additionFractions containing pure product
  5. extractionthen extracted with EtOAc
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-494c174124164157987e55922e3cf752
Source dataset
uspto-grants-2015_09
Patent number
US09126935B2

Reaction notes

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