Triethylamine → (2R,4S)-1-tert-butyl 2-methyl 4-(2-(2-methoxyphenyl)quinazolin-4-ylamino)pyrrolidine-1,2-dicarboxylate

HRID 2189210Notes

Reaction equation

HRID 2189210 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[O:18][CH3:19])[N:3]=1.[CH3:20][O:21][C:22]([C@H:24]1[CH2:28][C@H:27]([NH2:29])[CH2:26][N:25]1[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:23].C(N(CC)CC)C>O1CCOCC1.ClCCl>[CH3:19][O:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:4]1[N:3]=[C:2]([NH:29][C@@H:27]2[CH2:26][N:25]([C:30]([O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[O:31])[C@@H:24]([C:22]([O:21][CH3:20])=[O:23])[CH2:28]2)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 15194991-tert-Butyl 2-methyl (2R,4S)-4-aminopyrrolidine-1,2-dicarboxylateHCID 180716414-Chloro-2-(2-methoxyphenyl)quinazoline

Product 1

HCID 67365675(2R,4S)-1-tert-butyl 2-methyl 4-(2-(2-methoxyphenyl)quinazolin-4-ylamino)pyrrolidine-1,2-dicarboxylateYield 52%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

4-Chloro-2-(2-methoxyphenyl)quinazoline (0.463 g, 1.709 mmol), (2R,4S)-4-aminopyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (0.480 g, 1.709 mmol) and triethylamine (0.715 mL, 5.127 mmol) in dioxane (9 mL) were heated at reflux for 3 days. The mixture was cooled, diluted with dichloromethane (50 mL), and washed with water (50 mL). The organic extracts were dried (MgSO4) and concentrated. Purification by silica gel chromatography (10% methanol in dichloromethane) gave the title compound as a solid (0.423 g, 52%).

Workup

  1. temperatureat reflux for 3 days
  2. temperatureThe mixture was cooled
  3. washwashed with water (50 mL)
  4. dry with materialThe organic extracts were dried (MgSO4)
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-d1764fe517e745d6920331daa125631f
Source dataset
uspto-grants-2012_12
Patent number
US08324226B2

Reaction notes

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