4-Methylmorpholine → HCID 11340598, compound

HRID 1270982Notes

Reaction equation

HRID 1270982 reaction equation
C(O[C:6](=[O:24])[NH:7][C@H:8]([C:16](=[O:23])[NH:17][CH2:18][CH2:19][N:20]([CH3:22])[CH3:21])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)(C)(C)C.[CH:25]1[CH:26]=[CH:27][C:28]2[N:33](O)N=N[C:29]=2[CH:30]=1.CCN=C=N[CH2:40][CH2:41][CH2:42]N(C)C.[ClH:46].C(OC(N[C@@H:55]([CH2:59]C1C=CC=CC=1)[C:56](O)=[O:57])=O)(C)(C)C.CN(C)CCN.CN1CCOCC1>CN(C=O)C.CCOC(C)=O.O>[Cl:46][C:40]1[CH:41]=[CH:42][C:56]([O:57][C:25]2[CH:30]=[CH:29][C:28]([NH:33][C:6](=[O:24])[NH:7][C@@H:8]([CH2:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:16]([NH:17][CH2:18][CH2:19][N:20]([CH3:21])[CH3:22])=[O:23])=[CH:27][CH:26]=2)=[CH:55][CH:59]=1

Participants

10

Reactant 6

HCID 79724-MethylmorpholineHCID 66053N,N-DimethylethylenediamineHCID 757711-HydroxybenzotriazoleHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10936585HCID 10936585, compound

Product 1

HCID 11340598HCID 11340598, compoundYield 99%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

[(S)-1-(2-Dimethylamino-ethylcarbamoyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester. HOBT (1.4 g, 10.7 mmol) and EDCl (2 g, 10.7 mmol) were added to a solution of (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid (2 g, 7.2 mmol) in DMF (36 mL). Following the addition of a solution of N′,N′-dimethyl-ethane-1,2-diamine (0.946 g, 10.7 mmol) in DMF (5 mL), N-methyl-morpholine (1.5 g, 14.4 mmol) was added dropwise. The reaction mixture was stirred at rt overnight. Water (50 mL) and EtOAc (70 mL) were then added to the mixture. The aqueous layer was extracted with EtOAc (3×70 mL). The combined organic layers were washed with 1 N NaOH (2×50 mL) and brine (50 mL), dried (MgSO4), and concentrated. Purification by column chromatography [0–20% (1% NH4OH/MeOH)/CH2Cl2] afforded 2.5 g (99%) of the desired product. MS (electrospray): mass calculated for C18H29N3O3, 335.22; m/z found, 336.1 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.02 (s, 1H), 7.32–7.28 (m, 2H), 7.25–7.20 (m, 3H), 6.24 (s, 1H), 5.23 (d, J=6.5 Hz, 1H), 4.32–4.30 (m, 1H), 3.23–3.19 (m, 2H), 3.09 (dd, J=13.5, 6.3 Hz, 1H), 2.98 (dd, J=13.5, 6.3 Hz, 1H), 2.31–2.15 (m, 4H), 2.10 (s, 6H), 1.41 (s, 9H).

Workup

  1. additionwas added dropwise
  2. extractionThe aqueous layer was extracted with EtOAc (3×70 mL)
  3. washThe combined organic layers were washed with 1 N NaOH (2×50 mL) and brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customPurification by column chromatography [0–20% (1% NH4OH/MeOH)/CH2Cl2]

Sources & evidence

ORD record
ord-83407ce87b77495aa2ff55e0a5ca2b00
Source dataset
uspto-grants-2007_04
Patent number
US07202269B2

Reaction notes

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