Cesium carbonate → HCID 67298462, compound

HRID 1520400Notes

Reaction equation

HRID 1520400 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=3)[CH:10]=2)[N:5]=[C:4]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)[N:3]=1.[Cl:26][C:27]1[CH:28]=[C:29]([CH:34]2[CH2:38][NH:37][C:36](=[O:39])[CH2:35]2)[CH:30]=[CH:31][C:32]=1[Cl:33].C([O-])([O-])=O.[Cs+].[Cs+].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>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:26][C:27]1[CH:28]=[C:29]([CH:34]2[CH2:38][N:37]([C:2]3[C:11]4[C:6](=[CH:7][CH:8]=[C:9]([C:12]5[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=5)[CH:10]=4)[N:5]=[C:4]([C:20]4[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=4)[N:3]=3)[C:36](=[O:39])[CH2:35]2)[CH:30]=[CH:31][C:32]=1[Cl:33]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 17948975HCID 17948975, compoundHCID 86677088HCID 86677088, compound

Product 1

HCID 67298462HCID 67298462, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 4-chloro-6-(3-methoxyphenyl)-2-(pyridin-3-yl)quinazoline (40 mg, 0.12 mmol), 4-(3,4-dichlorophenyl)pyrrolidin-2-one (100 mg, 0.437 mmol) and Cs2CO3 (42 mg, 0.127 mmol) in dry toluene (6 mL) was added Pd(OAc)2 (3 mg, 0.01 mmol) and Xantphos (10 mg, 0.02 mmol) under a nitrogen atmosphere. The resulting mixture was stirred at 100° C. for 12 h. After cooling, the mixture was filtered through a pad of celite. The residue was purified by silica gel chromatography, eluted with petroleum ether/ethyl acetate (5:4) to give the desired product as a yellow solid. 14 mg of the desired product was obtained in a 22.5% yield, LCMS: retention time=1.802 min, [MH]+=541.0, 543.0. 1H-NMR (400 MHz, DMSO-d6): δ 9.73 (s, 1H), 9.05-9.04 (m, 1H), 8.86-8.85 (m, 1H), 8.42-8.38 (m, 2H), 8.19 (d, J=8.8 Hz, 1H), 7.89 (d, J=1.6 Hz, 1H), 7.82-7.81 (m, 1H), 7.69 (d, J=8.0 Hz, 1H), 7.58 (dd, J=8.0, 1.6 Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 7.41-7.36 (m, 2H), 7.07 (dd, J=8.0, 2.0 Hz, 1H), 4.57-4.46 (m, 2H), 4.06-4.03 (m, 1H), 3.20-3.01 (m, 2H), 3.88 (s, 3H).

Workup

  1. temperatureAfter cooling
  2. filtrationthe mixture was filtered through a pad of celite
  3. customThe residue was purified by silica gel chromatography
  4. washeluted with petroleum ether/ethyl acetate (5:4)

Sources & evidence

ORD record
ord-821d4b44020748938c46f39fed27e1e6
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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