Potassium Carbonate → HCID 71180950, compound

HRID 1520330Notes

Reaction equation

HRID 1520330 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)[N:6]=[C:5]2[NH:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[C:21]([Cl:26])[CH:20]=1.[N:27]1([CH2:32][CH2:33][CH2:34][NH2:35])[CH2:31][CH2:30][CH2:29][CH2:28]1.N1CCC[C@H]1C(O)=O.C(=O)([O-])[O-].[K+].[K+]>[Cu]I.O>[Cl:26][C:21]1[CH:20]=[C:19]([NH:18][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([NH:35][CH2:34][CH2:33][CH2:32][N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[CH:3]=3)[N:8]=[C:7]([C:12]3[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=3)[N:6]=2)[CH:24]=[CH:23][C:22]=1[F:25]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 316701-PyrrolidinepropanamineHCID 145742L-ProlineHCID 67298005HCID 67298005, compound

Product 1

HCID 71180950HCID 71180950, compoundYield 15.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A 2.0 dram reaction vial was charged with 6-bromo-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (synthesized as described in Scheme 1 and 4, substituting 5-bromo-2-nitrobenzoic acid for 2-nitro-5-propoxy-benzoic acid and 3-chloro-4-fluoroaniline for 2-aminobenzamide) (100 mg, 0.233 mmol, 1.0 equiv), 3-(pyrrolidin-1-yl)propan-1-amine (40 mg, 0.345 mmol, 1.5 equiv), copper(I) iodide (4.4 mg, 0.023 mmol, 0.1 equiv), L-proline (5.3 mg, 0.046 nm tool, 0.2 equiv), and potassium carbonate (96 mg, 0.69 mmol, 3.0 equiv) in 1DMF (3 mL). The reaction mixture was heated at 100° C. overnight. After cooling, water was added to the reaction mixture, and the resultant precipitate was collected by filtration. The crude product was purified via prep-TLC (silica, 2000 micron plate, 95% dichloromethane-5% methanol-0.1% NH4OH) to yield the desired compound as a brown solid (17.2 mg, 15%). LCMS m/z=477.4 (M+1) (Method C) (retention time=1.68 min). 1H NMR (300 MHz, DMSO) δ 9.68 (s, 1H), 9.46 (s, 1H), 8.59 (d, J=9.4 Hz, 2H), 8.25 (dd, J=6.8, 2.6 Hz, 1H), 7.93 (dd, J=8.3, 3.5 Hz, 1H), 7.69-7.59 (m, 1H), 7.52 (dd, J=11.0, 7.1 Hz, 2H), 7.36-7.19 (m, 2H), 6.41 (s, 1H), 3.34 (m, 2H) 2.69 (m, 6H), 2.02-1.82 (m, 2H), 1.75 (bs, 4H).

Workup

  1. customA 2.0 dram reaction
  2. temperatureAfter cooling
  3. filtrationthe resultant precipitate was collected by filtration
  4. customThe crude product was purified via prep-TLC (silica, 2000 micron plate, 95% dichloromethane-5% methanol-0.1% NH4OH)

Sources & evidence

ORD record
ord-8bf3cf22d8934ead8d1b5f3947093ce0
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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