Dimethyl Sulfoxide → HCID 11641110, compound

HRID 1865726Notes

Reaction equation

HRID 1865726 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][S:8]([CH3:10])=O.[F:11][C:12]([F:17])([F:16])[C:13]([OH:15])=[O:14].[OH:18][CH2:19]/[C:20](/[CH3:50])=[CH:21]/[C@@H:22]([N:26]([CH3:49])[C:27](=[O:48])[C@@H:28]([NH:33][C:34](=[O:47])[C@@H:35]([NH:45][CH3:46])[C:36]([CH3:44])([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH3:37])[C:29]([CH3:32])([CH3:31])[CH3:30])[CH:23]([CH3:25])[CH3:24].C(N(CC)CC)C>ClCCl>[F:11][C:12]([F:17])([F:16])[C:13]([OH:15])=[O:14].[CH3:7][S+:8]([CH3:10])[C:41]1[CH:42]=[CH:43][C:38]([C:36]([CH3:44])([CH3:37])[C@@H:35]([C:34]([NH:33][C@H:28]([C:27]([N:26]([C@@H:22]([CH:23]([CH3:24])[CH3:25])/[CH:21]=[C:20](\[CH3:50])/[CH:19]=[O:18])[CH3:49])=[O:48])[C:29]([CH3:30])([CH3:32])[CH3:31])=[O:47])[NH:45][CH3:46])=[CH:39][CH:40]=1.[CH3:46][NH:45][C@H:35]([C:34]([NH:33][C@H:28]([C:27]([N:26]([C@@H:22]([CH:23]([CH3:25])[CH3:24])/[CH:21]=[C:20](\[CH3:50])/[CH:19]=[O:18])[CH3:49])=[O:48])[C:29]([CH3:32])([CH3:31])[CH3:30])=[O:47])[C:36]([CH3:44])([CH3:37])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 69019819HCID 69019819, compound

Product 2

HCID 11641110HCID 11641110, compoundYield 129.9%HCID 87660263HCID 87660263, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
25 °C

Procedure

Following the procedure described in J. Org. Chem. 1994, 59(7), 1771, to a solution of oxalyl chloride (0.17 mmol) in dichloromethane at −78° C. is added a solution of dimethylsulfoxide (0.348 mmol, 0.025 mL) in dichloromethane dropwise. After 10 min a solution of (2S)-N-[(1S,2E)-4-hydroxy-1-isopropyl-3-methyl-2-butenyl]-N,3,3-trimethyl-2-{[(2S)-3-methyl-2-(methylamino)-3-phenylbutanoyl]amino}butanamide trifluoroacetic acid (83 mg, from Example 81) in dichloromethane is added dropwise. After 20 min triethylamine (0.725 mmol, 0.1 mL) is added dropwise. The reaction mixture is allowed to warm to 25° C. then washed with water and dried over anhydrous sodium sulfate. Concentration in vacuo and purification by reverse phase HPLC (0.01% aqueous trifluoroacetic acid/acetonitrile gradient system) gave the trifluoracetic acid salt of N,β,β-trimethyl-L-phenylalanyl-N1-[(1S,2E)-1-isopropyl-3-methyl-4-oxo-2-butenyl]-N1,3-dimethyl-L-valinamide as a white powder (43 mg) MS (ES): m/z 458.1 (M+H) and 4-(dimethylsulfonio)-N,β,β-trimethyl-L-phenylalanyl-N1-[(1S,2E)-1-isopropyl-3-methyl-4-oxo-2-butenyl]-N1,3-dimethyl-L-valinamide trifluoroacetate as a clear glass (28 mg) MS (ES): m/z 518.0 (M+).

Workup

  1. washthen washed with water
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationConcentration
  4. customin vacuo and purification by reverse phase HPLC (0.01% aqueous trifluoroacetic acid/acetonitrile gradient system)

Sources & evidence

ORD record
ord-f43a353e142d4020b8c88992cc2bdcf6
Source dataset
uspto-grants-2009_12
Patent number
US07626023B2

Reaction notes

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