4-Methylmorpholine → HCID 178512239, compound

HRID 1270979Notes

Reaction equation

HRID 1270979 reaction equation
C(O[C:6](=O)[NH:7][C@H:8]([C:16](=[O:26])[NH:17][CH2:18][CH2:19][CH2:20][N:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)(C)(C)C.CC[N:30]=[C:31]=[N:32]CCCN(C)C.Cl.[CH:40]1[CH:41]=[CH:42][C:43]2[N:48](O)N=N[C:44]=2[CH:45]=1.C(OC(N[C@@H](C[C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)C(O)=O)=O)(C)(C)C.N1(CCCN)CCCC1.CN1CCOCC1>CN(C=O)C.C(OCC)(=O)C>[C:40]1([C:63]2[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=2)[CH:45]=[CH:44][C:43]([N:48]=[C:6]([NH:32][C:31]#[N:30])[NH:7][C@@H:8]([CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:16]([NH:17][CH2:18][CH2:19][CH2:20][N:21]2[CH2:22][CH2:23][CH2:24][CH2:25]2)=[O:26])=[CH:42][CH:41]=1

Participants

9

Reactant 6

HCID 79724-MethylmorpholineHCID 316701-PyrrolidinepropanamineHCID 757711-HydroxybenzotriazoleHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69432098HCID 69432098, compound

Product 1

HCID 178512239HCID 178512239, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

[(S)-2-Phenyl-1-(3-pyrrolidin-1-yl-propylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester. To a mixture of EDCl (5.75 g, 30 mmol), HOBT (4.05 g, 30 mmol) and (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid (5.3 g, 20 mmol) in DMF (80 mL), was added 3-pyrrolidin-1-yl-propylamine (3.85 g, 30 mmol) in DMF (10 mL) followed by N-methylmorpholine (4.05 g, 40 mmol) in 10 mL of DMF at rt. The solution was stirred for 14 h and was diluted with ethyl acetate (500 mL). The organic layer was washed with saturated NaHCO3 (2×100 mL), brine (3×100 mL) and dried (Na2SO4). The solvent was removed, and the crude residue was stirred in a mixture of 10% EtOAc/hexanes for 1 h to afford 6.5 g (87%) of the desired product as a white solid. MS (electrospray): mass calculated for C21H33N3O3, 375.25, m/z found, 376.2 [M+H]+, 398.2 [M+Na]+. 1H NMR (400 MHz, CD3OD): 7.25–7.18 (m, 5H), 4.22 (t, J=3.6 Hz, 1H), 3.18–3.14 (m, 2H), 3.04 (dd, J=22.0, 6.5 Hz, 1H), 2.83 (dd, J=22.0, 8.3 Hz, 1H), 2.53–2.49 (m, 4H), 2.42 (t, J=7.9 Hz, 1H), 1.81–1.76 (m, 4H), 1.65–1.61 (m, 2H), 1.37 (s, 9H).

Workup

  1. washThe organic layer was washed with saturated NaHCO3 (2×100 mL), brine (3×100 mL)
  2. dry with materialdried (Na2SO4)
  3. customThe solvent was removed
  4. stirringthe crude residue was stirred in a mixture of 10% EtOAc/hexanes for 1 h

Sources & evidence

ORD record
ord-fc169c2e58be4bc18c512398713123af
Source dataset
uspto-grants-2007_04
Patent number
US07202269B2

Reaction notes

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