Bis-(1H-imidazol-2-YL)-methanone → (+)-2-{[4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-3-(1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-propionic acid methyl ester

HRID 1177736Notes

Reaction equation

HRID 1177736 reaction equation
[CH3:1][O:2][C:3](=[O:16])[CH:4]([NH2:15])[CH2:5][N:6]1[CH2:11][CH2:10][C:9]2[NH:12][N:13]=[CH:14][C:8]=2[CH2:7]1.[C:17](C1NC=CN=1)(C1NC=CN=1)=[O:18].[NH:29]1[CH2:34][CH2:33][CH:32]([N:35]2[CH2:44][C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[NH:37][C:36]2=[O:45])[CH2:31][CH2:30]1>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:16])[CH:4]([NH:15][C:17]([N:29]1[CH2:30][CH2:31][CH:32]([N:35]2[CH2:44][C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[NH:37][C:36]2=[O:45])[CH2:33][CH2:34]1)=[O:18])[CH2:5][N:6]1[CH2:11][CH2:10][C:9]2[NH:12][N:13]=[CH:14][C:8]=2[CH2:7]1

Participants

5

Reactant 3

HCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 110425973-(Piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-oneHCID 588644802-Amino-3-(1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-propionic acid methyl ester

Product 1

HCID 58864216(+)-2-{[4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-3-(1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-amino-3-(1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-propionic acid methyl ester (260 mg, 1 equiv) in methylene chloride (2 mL, 0° C.) was added carbonyl diimidazole (188 mg, 1 equiv). After 15 min, 3-piperidin-4-yl-3,4-dihydro-1H-quinazolin-2-one (295 mg, 1.1 equiv) was added in one portion. The ice bath was removed and stirring continued overnight. The reaction was concentrated and purified by column chromatography to give 118 mg (21%). 1H-NMR (CDCl3, 500 MHz) δ 1.60-1.80 (m, 4H), 2.70-3.05 (m, 8H), 3.45 (s, 2H), 3.56 (d, J=13.4, 1H), 3.62 (d, J=13.4, 1H), 3.75 (s, 3H), 4.02 (d, J=13.1, 1H), 4.10 (d, J=12.5, 1H), 4.24 (s, 2H), 4.45-4.57 (m, 2H), 5.79 (bs, 1H), 6.68 (d, J=7.94, 1H), 6.90 (dd, J=7.3, 7.3, 1H), 7.00 (d, J=7.3, 1H), 7.13 (dd, J=7.6, 7.3, 1H), 7.25 (s, 1H), 7.82 (s, 1H). Mass spec.: 482.27 (MH)+.

Workup

  1. customThe ice bath was removed
  2. concentrationThe reaction was concentrated
  3. custompurified by column chromatography
  4. customto give 118 mg (21%)

Sources & evidence

ORD record
ord-d789cbd37aec4114809723cf3ba28d4e
Source dataset
uspto-grants-2010_11
Patent number
US07842808B2

Reaction notes

Loading…