4-Methylmorpholine → Relacatib

HRID 229797Notes

Reaction equation

HRID 229797 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[S:7](Cl)(=[O:9])=[O:8].C(O[C:16](=[O:35])[NH:17][C@H:18]([C:23](=[O:34])[NH:24][C@H:25]1[CH2:31][CH2:30][C@@H:29]([CH3:32])[NH:28][CH2:27][C@@H:26]1[OH:33])[CH2:19][CH:20]([CH3:22])[CH3:21])(C)(C)C.C(OC(=O)N[C@H](C(=O)N[C@@H:50]1[CH2:56][CH2:55][C@H:54]([CH3:57])NC[C@H:51]1[OH:58])CC(C)C)(C)(C)C.CN1CCO[CH2:64][CH2:63]1>C(Cl)Cl.CCOC(C)=O>[CH3:22][CH:20]([CH3:21])[CH2:19][C@H:18]([NH:17][C:16]([C:63]1[O:58][C:51]2[CH:57]=[CH:54][CH:55]=[CH:56][C:50]=2[CH:64]=1)=[O:35])[C:23](=[O:34])[NH:24][C@H:25]1[CH2:31][CH2:30][C@@H:29]([CH3:32])[N:28]([S:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)(=[O:9])=[O:8])[CH2:27][C:26]1=[O:33]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 3787675Pyridine-2-sulfonyl ChlorideHCID 58665057[(S)-1-((3S,4S,7R)-3-hydroxy-7-methyl-azepan-4-ylcarbamoyl)-3-methyl-butyl]-carbamic acid tert-butyl esterHCID 69000626[(S)-1-((3R,4R,7S)-3-hydroxy-7-methyl-azepan-4-ylcarbamoyl)-3-methyl-butyl]-carbamic acid tert-butyl ester

Product 1

HCID 6918602RelacatibYield 64%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Pyridine sulfonyl chloride (0.6 g, 3.4 mmol) was added to a solution of [(S)-1-((3S,4S,7R)-3-Hydroxy-7-methyl-azepan-4-ylcarbamoyl)-3-methyl-butyl]-carbamic acid tert-butyl ester and [(S)-1-((3R,4R,7S)-3-hydroxy-7-methyl-azepan-4-ylcarbamoyl)-3-methyl-butyl]-carbamic acid tert-butyl ester (1.0 g, 2.8 mmol), N-methyl morpholine (0.45 ml, 4.1 mmol) in CH2Cl2 (35 ml) and was stirred at RT overnight. The reaction mixture was diluted with EtOAc (100 ml), washed with H2O, brine, dried with magnesium sulfate, filtered, concentrated in vacuo by rotary evaporation, and chromatographed (silica gel, 2.5% MeOH/CH2Cl2) to yield the title compound (0.9 g, 64%): 1H NMR: 8.68 (m, 1H), 8.05 (1H, d), 7.92 (1H, dd), 7.50 (1H, dd), 6.66 (1H, bd), 4.95-4.88 (dd), 4.20-3.87 (m, 3H), 3.65 (1H, bs), 3.40 (1H, d), 1.94-1.57 (m, 4H), 1.45-1.38 (m, 6H), 1.14 (3H, dd), 0.94 (6H, dd); Electrospray mass spec: M+H+=499.0

Workup

  1. washwashed with H2O, brine
  2. dry with materialdried with magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo by rotary evaporation
  5. customchromatographed (silica gel, 2.5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-62bc90c1bdf441ad893af19fe017f3c9
Source dataset
uspto-grants-2009_07
Patent number
US07563784B2

Reaction notes

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