Piperidine → HCID 68603501, compound

HRID 641962Notes

Reaction equation

HRID 641962 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][N:9]([C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=1[CH3:24])[C:18]([OH:20])=[O:19])[C:8]2=[O:25].[NH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1.C(N(CC)C(C)C)(C)C.[N-]=C=O>CC(N(C)C)=O.C(Cl)Cl>[CH3:24][C:23]1[CH:22]=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[CH:16][C:15]=1[N:9]1[C:8](=[O:25])[C:7]2[C:12](=[CH:13][CH:14]=[C:5]([O:4][CH2:3][CH2:2][N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)[CH:6]=2)[N:11]=[CH:10]1

Participants

7

Reactant 4

HCID 8082PiperidineHCID 81531DiisopropylethylamineHCID 105034IsocyanateHCID 68515557HCID 68515557, compound

Product 1

HCID 68603501HCID 68603501, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Procedure

To a stirred solution of 3-[6-(2-chloroethoxy)-4-oxoquinazolin-3(4H)-yl]-4-methylbenzoic acid (0.27 g), piperidine (0.3 ml), N,N-diisopropylethylamine (0.53 ml) and KI (0.25 g) in DMA (2 ml) was heated to 120° C. for 30 minutes in a microwave (Personal Chemistry Emrys Optimizer with 300 W magnetron). The reaction mixture was diluted with methylene chloride (20 ml), CombiZorb isocyanate resin (loading 1.03 mmol/g from Agilent) (5.75 g) added and stirred at room temperature for 16 hours. The resin was removed by filtration and the filtrate washed with water (50 ml). The aqueous phase 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 4-methyl-3-[4-oxo-6-(2-piperidin-1-ylethoxy)quinazolin-3(4H)-yl]benzoic acid (0.14 g); NMR Spectrum: (DMSOd6) 1.42 (m, 6H), 2.13 (s, 3H), 2.48 (m, 4H), 2.72 (m, 2H), 4.20 (m, 2H), 7.49 (m, 2H), 7.56 (m, 1H), 7.69 (d, 1H), 7.88 (s, 1H), 7.96 (d, 1H), 8.15 (s, 1H); Mass Spectrum: M+H+ 408.

Workup

  1. additionadded
  2. customThe resin was removed by filtration
  3. washthe filtrate washed with water (50 ml)
  4. customThe aqueous phase was purified by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK)
  5. additiona 99:1 mixture of methanol and aqueous ammonia solution

Sources & evidence

ORD record
ord-15d5e9b2d8cb45cc82fe74bc1827bb54
Source dataset
uspto-grants-2010_04
Patent number
US07696215B2

Reaction notes

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