Isopropyl iodide → HCID 68603382, compound

HRID 641986Notes

Reaction equation

HRID 641986 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[N:11]1[C:20](=[O:21])[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:22][C@H:23]3[CH2:27][CH2:26][NH:25][CH2:24]3)[CH:18]=2)[N:13]=[CH:12]1.C(=O)([O-])[O-].[K+].[K+].[CH:34](I)([CH3:36])[CH3:35].[OH-].[Na+]>CC(N(C)C)=O.O.CO>[CH:34]([N:25]1[CH2:26][CH2:27][C@H:23]([O:22][C:17]2[CH:18]=[C:19]3[C:14](=[CH:15][CH:16]=2)[N:13]=[CH:12][N:11]([C:3]2[CH:4]=[C:5]([CH:9]=[CH:10][C:2]=2[CH3:1])[C:6]([OH:8])=[O:7])[C:20]3=[O:21])[CH2:24]1)([CH3:36])[CH3:35]

Participants

8

Reactant 4

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 68603925HCID 68603925, compound

Product 1

HCID 68603382HCID 68603382, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
50 °C

Procedure

4-methyl-3-[4-oxo-6-[(3S)-pyrrolidin-3-yloxy]quinazolin-3(4H)-yl]benzoic acid (0.21 g) isopropyliodide (0.073 ml), and potassium carbonate (0.318 g) were stirred in dimethylacetamide (2 ml) for 18 hours at room temperature. Additional isopropyliodide (0.073 ml) was added and stirring continued for a further 24 hours. To the reaction mixture was added MeOH (2 ml), water (0.5 ml) and 2N NaOH (0.58 ml) and the reaction mixture was heated at 50° C. for 18 hours. The reaction mixture was purified by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK) using initially methanol and then a 99:1 mixture of methanol and aqueous ammonia solution to give a brown oil which solidified on standing for 18 hours in vacuo to give 3-[6-{[(3S)-1-isopropylpyrrolidin-3-yl]oxy}-4-oxoquinazolin-3(4H)-yl]-4-methylbenzoic acid (297 mg); NMR Spectrum: (DMSOd6) 0.99 (m, 6H), 1.80 (m, 1H), 2.13 (s, 3H), 2.33 (m, 2H), 2.78 (m, 4H), 5.03 (m, 1H), 7.46 (m, 3H), 7.70 (d, 1H), 7.87 (s, 1H), 7.96 (d, 1H), 8.16 (s, 1H); Mass Spectrum: M+H+ 408.

Workup

  1. customThe reaction mixture was purified by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK)
  2. additiona 99:1 mixture of methanol and aqueous ammonia solution
  3. customto give a brown oil which
  4. waiton standing for 18 hours in vacuo

Sources & evidence

ORD record
ord-300637482ba54cf1b585a6628de339c3
Source dataset
uspto-grants-2010_04
Patent number
US07696215B2

Reaction notes

Loading…