4-Methylmorpholine → {(S)-1-[3-hydroxy-6-methyl-1-(pyridine-2-sulfonyl)-azepan-4-ylcarbamoyl]-3-methyl-butyl}-carbamic acid tert-butyl ester

HRID 229787Notes

Reaction equation

HRID 229787 reaction equation
Cl.[NH2:2][CH:3]1[CH2:9][CH:8]([CH3:10])[CH2:7][N:6]([S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)(=[O:13])=[O:12])[CH2:5][CH:4]1[OH:20].[NH:21]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C@H:22]([C:27](O)=[O:28])[CH2:23][CH:24]([CH3:26])[CH3:25].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CN(C=O)C>[C:33]([O:32][C:30](=[O:31])[NH:21][C@H:22]([C:27](=[O:28])[NH:2][CH:3]1[CH2:9][CH:8]([CH3:10])[CH2:7][N:6]([S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)(=[O:13])=[O:12])[CH2:5][CH:4]1[OH:20])[CH2:23][CH:24]([CH3:25])[CH3:26])([CH3:34])([CH3:36])[CH3:35]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 689985504-Amino-6-methyl-1-(pyridine-2-sulfonyl)-azepan-3-ol HCl salt

Product 1

HCID 11496976{(S)-1-[3-hydroxy-6-methyl-1-(pyridine-2-sulfonyl)-azepan-4-ylcarbamoyl]-3-methyl-butyl}-carbamic acid tert-butyl esterYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Amino-6-methyl-1-(pyridine-2-sulfonyl)-azepan-3-ol HCl salt (0.21 g, 0.59 mmol) was dissolved in 5 ml DMF. To this solution, was added Boc-Leu-OH (0.22 g, 0.88 mmol) and HBTU (0.34 g, 0.90 mmol) and then NMM (0.24 g, 2.4 mmol). The mixture was stirred at RT overnight. DMF was removed under high vacuum. The residue was diluted in EtOAc and washed with H2O, 10% NaHCO3 and brine. Purification by column chromatography gave the title compound (0.2 g, 68% yield). MS (M+H+): 499.1; 1H-NMR (400 Hz, CDCl3): 8.75(d, 1H), 8.0-7.75(m, 2H), 7.5 5(m, 1H) 5.10(m, 1H), 4.15-2.90(m, 10H), 2.10-1.48(m, 14H), 1.00(m, 9H)

Workup

  1. customDMF was removed under high vacuum
  2. additionThe residue was diluted in EtOAc
  3. washwashed with H2O, 10% NaHCO3 and brine
  4. customPurification by column chromatography

Sources & evidence

ORD record
ord-1f493372156f402790edfa1d49e0a928
Source dataset
uspto-grants-2009_07
Patent number
US07563784B2

Reaction notes

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