4(3H)-Quinazolinone, 6-chloro-3-methyl- → HCID 71254821, compound

HRID 1507643Notes

Reaction equation

HRID 1507643 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1[CH:13]=[C:12]([NH:14][C:15]([C:17]2NC(C(F)(F)F)=N[C:21]=2[C:22]2[CH:27]=[CH:26]C(F)=CC=2)=O)[CH:11]=[CH:10][C:9]=1C)([CH3:4])([CH3:3])[CH3:2].ClC1C=C2C(=CC=1)[N:42]=[CH:41][N:40]([CH3:46])[C:39]2=[O:47].C[O-].[Na+].[CH:51]1C=CC2N=CNC(=O)C=2C=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O.C1(C)C=CC=CC=1>[CH3:51][C:11]1[CH:10]=[CH:9][C:8]([NH:7][C:6](=[O:34])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:13][C:12]=1[NH:14][C:15]1[CH:17]=[C:21]2[C:22](=[CH:27][CH:26]=1)[N:42]=[CH:41][N:40]([CH3:46])[C:39]2=[O:47]

Participants

8

Reactant 4

HCID 632054(3H)-Quinazolinone, 6-chloro-3-methyl-HCID 10942334Sodium MethoxideHCID 71254960HCID 71254960, compoundHCID 1354087534(1H)-Quinazolinone

Product 1

HCID 71254821HCID 71254821, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To refluxing toluene (50 mL) in a 150 mL round bottom flask was added 2-methyl-5-t-butylcarbamate aniline 23 (3 g, 13.50 mmol, 1.2 eq), -chloro-3-methyl-4-oxoquinazoline 28 (2.19 g, 11.25 mmol, 1 eq), NaOMe (1.51 g, 15.75 mmol, 1.4 eq), and 2-diphenylbistbutylphosphine (168 mg, 5 mol %, 0.561 mmol), and Pd2(dba)3 (309 mg, 3 mol %, 0.336 mmol). This mixture was refluxed for 8 hours when it was observed there was complete amination of quinazolinone starting material. The reaction mixture was cooled to room temperature and poured into 250 mL EtOAc and then washed with sodium bicarbonate (2×100 mL), water (2×100 mL), and then brine (2×100 mL). The light brown solid was then purified by flash chromatography on silica (70% EtOAc/Hex) to yield desired product 29 as a light yellow solid (3.6 g, 9.33 mmol, 83% yield). 1H NMR (300 MHz, D6 DMSO): δ 7.91 (s, 1H), 7.64 (d, 1H, J=2.7 Hz), 7.61 (s, 1H, J=8.8 Hz), 7.34 (dd, 1H, J=2.7 Hz, J=8.8 Hz), 7.29 (s, 1H), 7.16 (d, 1H, J=8.2 Hz), 7.09 (d, 1H, J=8.2 Hz), 6.47 (s, 1H), 5.70 (s, 1H), 3.59 (s, 3H), 1.64 (s, 3H), 1.51 (s, 9H). 13C NMR (75 MHz, D6 DMSO): δ 161.34, 153.57, 145.59, 145.58, 141.04, 139.09, 131.84, 129.01, 125.35, 123.96, 123.24, 114.31, 112.49, 108.33, 79.70, 34.26, 28.97, 18.14. ESMS: m/z 381.2 [MH]+

Workup

  1. temperatureThis mixture was refluxed for 8 hours when it
  2. washwashed with sodium bicarbonate (2×100 mL), water (2×100 mL)
  3. customThe light brown solid was then purified by flash chromatography on silica (70% EtOAc/Hex)

Sources & evidence

ORD record
ord-741d1330d0eb463daf65f319d073c768
Source dataset
uspto-grants-2015_12
Patent number
US09221805B2

Reaction notes

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