4-Methylmorpholine → [(S)-1-(2-{(4-Bromophenyl)-[(E)-(3-phenylacryloyl)]amino}acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl ester

HRID 2243985Notes

Reaction equation

HRID 2243985 reaction equation
C(N=C=NCCCN(C)C)C.[Br:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]([CH2:30][C:31]([OH:33])=O)[C:20](=[O:29])/[CH:21]=[CH:22]/[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:15][CH:14]=1.[C:34]([O:38][C:39]([NH:41][C@H:42]1[CH2:46][CH2:45][NH:44][CH2:43]1)=[O:40])([CH3:37])([CH3:36])[CH3:35].ON1C2N=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C>[Br:12][C:13]1[CH:14]=[CH:15][C:16]([N:19]([C:20](=[O:29])/[CH:21]=[CH:22]/[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:30][C:31]([N:44]2[CH2:45][CH2:46][C@H:42]([NH:41][C:39](=[O:40])[O:38][C:34]([CH3:36])([CH3:35])[CH3:37])[CH2:43]2)=[O:33])=[CH:17][CH:18]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 59212055HCID 59212055, compound

Product 1

HCID 59211949[(S)-1-(2-{(4-Bromophenyl)-[(E)-(3-phenylacryloyl)]amino}acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-Ethyl-3-(3′-dimethylaminopropyl)carbodiimide (9.39 g, 0.049 mol) was added to a solution of {(4-Bromophenyl)-[(E)-(3-phenylacryloyl)]amino}acetic acid 2 (13.82 g, 0.038 mol), (3S)-(−)-3-(tert-butoxycarbonylamino)pyrrolidine (9.13 g, 0.049 mol), 1-hydroxy-7-azabenzotriazole (6.67 g, 0.049 mol) and N-methylmorpholine (8.4 mL, 0.08 mol) in DMF (150 ml). The reaction mixture was stirred at room temperature for 16 h and then concentrated in vacuo. The residue was diluted with ethyl acetate and washed with 10% hydrochloric acid (×3), brine, saturated aqueous sodium bicarbonate (×2) and brine. The title compound began to crystallize during work-up and was collected by filtration. The mother liquor was concentrated to provide a further quantity of product. Total yield of title compound: 17.43 g, 86%. 1HNMR (300 MHz) (CDCl3) δ 1.45 (6H, s), 1.60 (3H, s), 1.7-2.3 (2H, m), 3.4-3.8 (4H, m), 4.1-4.9 (3H, m), 6.36 (1H, d, J=16 Hz), 7.36 (2H, d), 7.2-7.4 (5H, m), 7.55 (2H, d) and 7.70 (1H, d, J=16 Hz).

Workup

  1. concentrationconcentrated in vacuo
  2. additionThe residue was diluted with ethyl acetate
  3. washwashed with 10% hydrochloric acid (×3), brine, saturated aqueous sodium bicarbonate (×2) and brine
  4. customto crystallize during work-up
  5. filtrationwas collected by filtration
  6. concentrationThe mother liquor was concentrated
  7. customto provide a further quantity of product

Sources & evidence

ORD record
ord-b94329b68bcb407eb5732c970feb769d
Source dataset
uspto-grants-2010_03
Patent number
US07678785B2

Reaction notes

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