(6-Cyclopentyloxy-pyridin-3-yl)-carbamic acid 4-nitro-phenyl ester → 4-(6,7-Dimethoxy-quinazolin-4-yl)-piperidine-1-carboxylic acid (6-cyclopentyloxy-pyridin-3-yl)-amide

HRID 657248Notes

Reaction equation

HRID 657248 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:34]=[N:35][C:36]([O:39][CH:40]3[CH2:44][CH2:43][CH2:42][CH2:41]3)=[CH:37][CH:38]=2)=CC=1)([O-])=O>C(Cl)Cl>[CH:40]1([O:39][C:36]2[N:35]=[CH:34][C:33]([NH:32][C:31]([N:18]3[CH2:19][CH2:20][CH:15]([C:6]4[C:5]5[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=5)[N:9]=[CH:8][N:7]=4)[CH2:16][CH2:17]3)=[O:30])=[CH:38][CH:37]=2)[CH2:41][CH2:42][CH2:43][CH2:44]1

Participants

4

Reactant 2

HCID 58770029(6-Cyclopentyloxy-pyridin-3-yl)-carbamic acid 4-nitro-phenyl esterHCID 595517346,7-Dimethoxy-4-(piperidin-4-yl)quinazoline

Product 1

HCID 587707204-(6,7-Dimethoxy-quinazolin-4-yl)-piperidine-1-carboxylic acid (6-cyclopentyloxy-pyridin-3-yl)-amideYield 29%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 6,7-dimethoxy-4-piperidin-4-yl-quinazoline (12 mg, 0.044 mmol), prepared as described in Example 1d, (6-cyclopentyloxy-pyridin-3-yl)-carbamic acid 4-nitro-phenyl ester (20 mg, 0.058 mmol), prepared as described in the previous step, and DCM (500 uL) was treated with TEA (6 uL, 0.043 mmol) in one portion at rt. The homogeneous amber solution was stirred at rt for 2 h, diluted with DCM (2 mL), and washed with H2O (2 mL). The aqueous layer was extracted with DCM (2×2 mL), the organic layers were combined, dried (Na2SO4) and concentrated in vacuo. Purification by prep tlc (1:9 MeOH/DCM) afforded the title compound (6.0 mg, 29%). 1H-NMR (300 MHz, CDCl3): δ 9.10 (s, 1H), 8.08 (s, 1H), 7.89 (d, 1H), 7.39 (s, 1H), 7.28 (s, 1H), 6.71 (d, 1H), 6.61 (bs, 1H), 5.30 (m, 1H), 4.32 (d, 2H), 4.08 (s, 6H), 3.62 (m, 1H), 3.20 (m, 2H), 2.16 (m, 2H), 1.98 (m, 4H), 1.79 (m, 4H), 1.62 (m, 2H). LC/MS (ESI) calcd for C26H31N5O4 477.56, found [M+1]+ 478.1.

Workup

  1. customprepared
  2. customprepared
  3. washwashed with H2O (2 mL)
  4. extractionThe aqueous layer was extracted with DCM (2×2 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customPurification by prep tlc (1:9 MeOH/DCM)

Sources & evidence

ORD record
ord-cea777b775994be18d3fff16c3d26d85
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Reaction notes

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