Water → HCID 59222959, compound

HRID 2386908Notes

Reaction equation

HRID 2386908 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:3]=1[C:4]([NH:13][CH2:14][CH2:15][C:16]1[CH:17]=[CH:18][C:19]([O:23][C:24]3[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][N:25]=3)=[C:20]([OH:22])[CH:21]=1)=[N:5][CH:6]=[N:7]2.I[CH2:35][CH2:36][CH3:37].C([O-])([O-])=O.[K+].[K+].O>CS(C)=O>[F:1][C:2]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:3]=1[C:4]([NH:13][CH2:14][CH2:15][C:16]1[CH:17]=[CH:18][C:19]([O:23][C:24]3[CH:29]=[C:28]([C:30]([F:33])([F:31])[F:32])[CH:27]=[CH:26][N:25]=3)=[C:20]([O:22][CH2:35][CH2:36][CH3:37])[CH:21]=1)=[N:5][CH:6]=[N:7]2

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 336431-IodopropaneHCID 59222981HCID 59222981, compound

Product 1

HCID 59222959HCID 59222959, compoundYield 63.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 5-[2-(5,8-difluoroquinazolin-4-ylamino)-ethyl]-2-(4-trifluoromethylpyridin-2-yloxy)-phenol (0.462 g, 0.5 mmol) in DMSO (5 mL) was added 1-iodopropane (0.204 g, 1.2 mmol) and K2CO3 (0.207 g, 1.5 mmol). The reaction mixture was stirred at 50° C. overnight and then at 70° C. for another 24 h. After cooling to room temperature, the mixture was poured into water and the gum-like material was separated via suction filtration and washed with water. The gum-like product then was partitioned between CH2Cl2 and brine. The organic phase was dried over sodium sulfate and concentrated in vacuo, and the product was purified by preparative reverse phase HPLC to give 0.161 g (32%) of (5,8-difluoroquinazolin-4-yl)-{2-[3-propoxy-4-(4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethyl}-amine as a brown gum; MS m/z 504. 1H NMR (CDCl3): δ 8.68 (s, 1H), 8.26 (d, J=4.8 Hz, 1H), 7.33 (m, 1H), 7.08-7.15 (m, 3H), 6.87-7.03 (m, 3H), 6.70-6.83 (br, 1H), 3.89-3.97 (m, 2H), 3.80-3.86 (m, 2H), 3.02 (t, J=6.9 Hz, 2H), 1.51 (m, 2H), 0.66 (t, J=7.2 Hz, 3H). LC/MS: 506.10 (M++1).

Workup

  1. waitat 70° C. for another 24 h
  2. temperatureAfter cooling to room temperature
  3. customthe gum-like material was separated via suction filtration
  4. washwashed with water
  5. customThe gum-like product then was partitioned between CH2Cl2 and brine
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customthe product was purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-922fcf9af88c4893a2021d51b9166136
Source dataset
uspto-grants-2012_09
Patent number
US08268843B2

Reaction notes

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