4-Methylmorpholine → HCID 10459847, compound

HRID 1270981Notes

Reaction equation

HRID 1270981 reaction equation
C(O[C:6](=[O:28])[NH:7][C@H:8]([C:16](=[O:27])[NH:17][CH2:18][CH2:19][N:20]([CH:24]([CH3:26])[CH3:25])[CH:21]([CH3:23])[CH3:22])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)(C)(C)C.[CH:29]1[CH:30]=[CH:31][C:32]2[N:37](O)N=N[C:33]=2[CH:34]=1.CCN=C=N[CH2:44][CH2:45][CH2:46]N(C)C.[ClH:50].C(OC(N[C@@H:59]([CH2:63]C1C=CC=CC=1)[C:60](O)=[O:61])=O)(C)(C)C.C(N(C(C)C)CCN)(C)C.CN1CCOCC1>CN(C=O)C.CCOC(C)=O.O>[Cl:50][C:44]1[CH:45]=[CH:46][C:60]([O:61][C:29]2[CH:34]=[CH:33][C:32]([NH:37][C:6](=[O:28])[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]([CH:21]([CH3:22])[CH3:23])[CH:24]([CH3:25])[CH3:26])=[O:27])=[CH:31][CH:30]=2)=[CH:59][CH:63]=1

Participants

10

Reactant 6

HCID 79724-MethylmorpholineHCID 84591,2-Ethanediamine, N1,N1-bis(1-methylethyl)-HCID 757711-HydroxybenzotriazoleHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 52877826HCID 52877826, compound

Product 1

HCID 10459847HCID 10459847, compoundYield 72%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

[(S)-1-(2-Diisopropylamino-ethylcarbamoyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester. HOBT (1.2 g, 8.49 mmol) and EDCl (1.6 g, 8.49 mmol) were added to a solution of (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid in DMF (11 mL). Following the addition of a solution of N′,N′-diisopropyl-ethane-1,2-diamine (0.978 g, 6.8 mmol) in DMF (2 mL), N-methyl-morpholine (1.1 g, 11.3 mmol) was added dropwise. The reaction mixture was stirred at rt overnight. Water (20 mL) and EtOAc (30 mL) were then added to the mixture. The aqueous layer was extracted with EtOAc (3×30 mL). The combined organic layers were washed sequentially with 1 N NaOH (2×20 mL) and brine (40 mL), and dried (MgSO4). The solvents were removed. The crude product was purified by column chromatography [0–20% (1% NH4OH/MeOH)/CH2Cl2] to afford 1.6 g (72%) of the desired product. MS (electrospray): mass calculated for C22H37N3O3, 391.55; m/z found, 392.3 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.57 (s, 1H), 7.36–7.29 (m, 2H), 7.26–7.21 (m, 3H), 3.62–3.55 (m, 1H), 3.49 (d, J=5.5 Hz, 1H), 3.27 (dd, J=4.1, 13.6 Hz, 1H), 3.24 (d, J=6.2 Hz, 1H), 3.22 (d, J=6.1 Hz), 3.02–2.95 (m, 2H), 2.67 (dd, J=13.6, 9.4 Hz, 1H), 2.54 (t, J=6.3 Hz, 2H), 1.67 (s, 1H), 1.24 (d, J=5.6 Hz, 2H), 0.98 (d, J=6.6 Hz, 12H).

Workup

  1. additionwas added dropwise
  2. extractionThe aqueous layer was extracted with EtOAc (3×30 mL)
  3. washThe combined organic layers were washed sequentially with 1 N NaOH (2×20 mL) and brine (40 mL)
  4. dry with materialdried (MgSO4)
  5. customThe solvents were removed
  6. customThe crude product was purified by column chromatography [0–20% (1% NH4OH/MeOH)/CH2Cl2]

Sources & evidence

ORD record
ord-4e473ac0d0db4859bde548a09d0f53fb
Source dataset
uspto-grants-2007_04
Patent number
US07202269B2

Reaction notes

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