Triethylamine → (2R,4S)-tert-Butyl 2-(dimethylcarbamoyl)-4-(2-(2-methoxyphenyl)quinazolin-4-ylamino)pyrrolidine-1-carboxylate

HRID 2189212Notes

Reaction equation

HRID 2189212 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([NH:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]=[C:16]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[O:30][CH3:31])[N:15]=2)[CH2:10][C@@H:9]1[C:32]([OH:34])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:36][NH:37][CH3:38].[B-](F)(F)(F)F.CN(C(ON1N=NC2C1=CC=CC=2)=[N+](C)C)C.C(N(CC)CC)C>CN(C=O)C.O>[CH3:36][N:37]([CH3:38])[C:32]([C@H:9]1[CH2:10][C@H:11]([NH:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]=[C:16]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[O:30][CH3:31])[N:15]=2)[CH2:12][N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[O:34]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67366705(2R,4S)-1-(tert-Butoxycarbonyl)-4-(2-(2-methoxyphenyl)quinazolin-4-ylamino)pyrrolidine-2-carboxylic acid

Product 1

HCID 67366947(2R,4S)-tert-Butyl 2-(dimethylcarbamoyl)-4-(2-(2-methoxyphenyl)quinazolin-4-ylamino)pyrrolidine-1-carboxylateYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of (2R,4S)-1-(tert-butoxycarbonyl)-4-(2-(2-methoxyphenyl)quinazolin-4-ylamino)pyrrolidine-2-carboxylic acid (0.095 g, 0.204 mmol), dimethylamine hydrochloride (0.017 g, 0.204 mmol), 0-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (0.077 g, 0.204 mmol), and triethylamine (0.037 mL, 0.265 mmol) in DMF (1 mL) was stirred for 24 hours. Water (20 mL) was added and the aqueous layer was extracted with ethyl acetate (3×20 mL). The organic extracts were combined, dried (MgSO4) and concentrated. Purification by silica gel chromatography (10% methanol in dichloromethane) gave the title compound as a solid (0.090 g, 90%).

Workup

  1. extractionthe aqueous layer was extracted with ethyl acetate (3×20 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customPurification by silica gel chromatography (10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-cf4c8a443031465dadbd2fc3034c041c
Source dataset
uspto-grants-2012_12
Patent number
US08324226B2

Reaction notes

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