Dimethylformamide → HCID 135939046, compound

HRID 591706Notes

Reaction equation

HRID 591706 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:17][C:16](=[O:18])[C:15]3[C:10](=[CH:11][C:12]([O:21][CH3:22])=[CH:13][C:14]=3[O:19][CH3:20])[N:9]=2)=[CH:4][CH:3]=1.[NH2:23][C:24]1[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=1.C([O-])([O-])=O.[Cs+].[Cs+].CN(C=O)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH3:20][O:19][C:14]1[CH:13]=[C:12]([O:21][CH3:22])[CH:11]=[C:10]2[C:15]=1[C:16](=[O:18])[NH:17][C:8]([C:5]1[CH:6]=[CH:7][C:2]([NH:23][C:24]3[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=3)=[CH:3][CH:4]=1)=[N:9]2

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 100093-AminopyridineHCID 10796Cesium carbonateHCID 136348046HCID 136348046, compound

Product 1

HCID 135939046HCID 135939046, compoundYield 51%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-(4-bromophenyl)-5,7-dimethoxyquinazolin-4(3H)-one (0.200 g, 0.55 mmol), 3-aminopyridine (0.057 g, 0.61 mmol), Cs2CO3 (0.253 g, 0.776 mmol), Xantphos (0.002 g, 0.003 mmol), and Pd2(dba)3 (0.003 g, 0.003 mmol) in dioxane (2 mL) were combined in a microwave tube under nitrogen and irradiated at 300 W, 105° C. for 30 minutes. Then, DMF (1 mL) was added and the flask was irradiated for 1 hour at 300 W, 105° C. Then, the mixture was concentrated and purified by silica gel chromatography, eluting with 92:7:1 CHCl3/MeOH/concentrated NH4OH. The residue was further purified by reverse-phase HPLC, eluting with 10% to 90% CH3CN in H2O with 0.1% TFA, to afford the title compound (0.105 g, 51%) as a white solid. 1H NMR (300 MHz, DMSO-d6): δ 11.83 (s, 1H), 8.82 (s, 1H), 8.44 (d, J=2.4 Hz, 1H), 8.11-8.16 (m, 3H), 7.59-7.62 (m, 1H), 7.31-7.35 (m, 1H), 7.13 (d, J=8.7 Hz, 2H), 6.68 (d, J=1.8 Hz, 1H), 6.46 (d, J=1.8 Hz, 1H), 3.88 (s, 3H), 3.83 (s, 3H). APCI MS m/z 375 [M+H]+.

Workup

  1. customwere combined in a microwave tube under nitrogen
  2. customirradiated at 300 W, 105° C. for 30 minutes
  3. customthe flask was irradiated for 1 hour at 300 W, 105° C
  4. concentrationThen, the mixture was concentrated
  5. custompurified by silica gel chromatography
  6. washeluting with 92:7:1 CHCl3/MeOH/concentrated NH4OH
  7. customThe residue was further purified by reverse-phase HPLC
  8. washeluting with 10% to 90% CH3CN in H2O with 0.1% TFA

Sources & evidence

ORD record
ord-b8178513a394408c89950a339c08144d
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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