(4-Isopropylphenyl)-carbamic acid 4-nitrophenyl ester → 4-(6,7-Dimethoxy-quinazolin-4-yl)-piperidine-1-carboxylic acid (4-isopropyl-phenyl)-amide

HRID 657191Notes

Reaction equation

HRID 657191 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.[N+](C1C=CC([O:30][C:31](=O)[NH:32][C:33]2[CH:38]=[CH:37][C:36]([CH:39]([CH3:41])[CH3:40])=[CH:35][CH:34]=2)=CC=1)([O-])=O>CC#N>[CH:39]([C:36]1[CH:37]=[CH:38][C:33]([NH:32][C:31]([N:18]2[CH2:19][CH2:20][CH:15]([C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][N:7]=3)[CH2:16][CH2:17]2)=[O:30])=[CH:34][CH:35]=1)([CH3:41])[CH3:40]

Participants

4

Reactant 2

HCID 46186565(4-Isopropylphenyl)-carbamic acid 4-nitrophenyl esterHCID 595517346,7-Dimethoxy-4-(piperidin-4-yl)quinazoline

Product 1

HCID 587708034-(6,7-Dimethoxy-quinazolin-4-yl)-piperidine-1-carboxylic acid (4-isopropyl-phenyl)-amideYield 72%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 6,7-dimethoxy-4-piperidin-4-yl-quinazoline (18.8 mg, 68.9 μmol), as prepared in Example 1d, and (4-isopropyl-phenyl)-carbamic acid 4-nitro-phenyl ester 21.3 mg, 71.0 μmol), as prepared in the preceding step, was stirred in CH3CN (250 μL) at 80° C. for 4 h. The reaction was then partitioned with DCM (4 mL) and 1 M K2CO3 (4 mL), and the organic layer was dried (Na2SO4) and concentrated under reduced pressure. Flash chromatography of the residue (EtOAc) provided the title compound (21.5 mg, 72%). 1H-NMR (300 MHz, CDCl3) δ 9.08 (s, 1H), 7.34 (s, 1H), 7.31-7.25 (m, 3H), 7.16 (m, 2H), 6.37 (br s, 1H), 4.32-4.22 (m, 2H), 4.07 (s, 3H), 4.06 (s, 3H), 3.60 (tt, 1H), 3.18 (td, 2H), 2.87 (heptet, 1H), 2.24-2.08 (m, 2H), 2.04-1.94 (m, 2H), 1.23 (d, 6H). LC/MS (ESI): calcd mass 434.2, found 435.3 (MH)+.

Workup

  1. customas prepared in the preceding step
  2. customThe reaction was then partitioned with DCM (4 mL) and 1 M K2CO3 (4 mL)
  3. dry with materialthe organic layer was dried (Na2SO4)
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-40bcfa2f515141b386d386793e6abed8
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Reaction notes

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