Dimethyl Sulfoxide → HCID 9983037, compound

HRID 750383Notes

Reaction equation

HRID 750383 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH:12]([C@@H:24]([NH:34][C:35](=[O:45])[O:36][C@H:37]1[C:41]([CH3:43])([CH3:42])[CH2:40][O:39][C:38]1=[O:44])[CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([NH:32][CH3:33])=[O:31])[C:13](=[O:23])[NH:14][C@@H:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:16].C(N(CC)CC)C>ClCCl>[CH3:33][NH:32][C:30]([NH:29][CH2:28][CH2:27][CH2:26][CH2:25][C@H:24]([NH:34][C:35](=[O:45])[O:36][C@H:37]1[C:41]([CH3:42])([CH3:43])[CH2:40][O:39][C:38]1=[O:44])[C:12](=[O:11])[C:13](=[O:23])[NH:14][C@@H:15]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH3:16])=[O:31]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 59752257HCID 59752257, compound

Product 1

HCID 9983037HCID 9983037, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of oxalylchloride (0.058 mL, 0.67 mmol) in anhydrous dichloromethane (2 mL) was cooled to −60° C. under nitrogen. Anhydrous dimethylsulfoxide (0.095 mL, 1.34 mmol) was then added dropwise, and the resulting solution was stirred for 10 min. A solution of (3S)-4,4-dimethyl-2-oxotetrahydro-3-furanyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)-5-{[(methylamino)carbonyl]amino}pentylcarbamate (150 mg, 0.30 mmol) in dichloromethane (3 mL) was then added. After 15 min, triethylamine (0.212 mL, 1.52 mmol) was added to the reaction mixture, which was kept cold for 2 min. and then allowed to warm to room temperature. After 40 min, the reaction mixture was subjected directly to column chromatography on silica gel. Elution with 10% acetone in ethyl acetate afforded (3S)-4,4-dimethyl-2-oxotetrahydro-3-furanyl (1S)-5-{[(methylamino)carbonyl]amino}-1-(oxo{[(1R)-1-phenylethyl]amino}acetyl)pentylcarbamate as a colorless gum after drying under vacuum (82 mg, 56%). 1H NMR (300 MHz, DMSO-d6) δ 9.26 (d, J=8 Hz, 1H); 7.99 (d, J=8 Hz, 1H); 7.40-7.33 (m, 4H); 7.31-7.23 (m, 1H); 5.92-5.84 (m, 1H); 5.71-5.63 (m, 1H); 5.40 (s, 1H); 5.08-4.96 (m, 1H); 4.85-4.78 (m, 1H); 4.16 (1/2Abq, J=8 Hz, 1H); 4.06 (1/2Abq, J=8 Hz, 1H); 3.04-2.91 (m, 2H); 2.55 (part of d overlapping DMSO, 3H); 1.74-1.61 (m, 1H); 1.46 (d, J=7 Hz, 1H); 1.45-1.29 (m, 5H); 1.12 (s, 1H); 1.05 (s, 1H). ES-LCMS m/493 (M+H) HRMS C24H34N4O7 m/491.2505 (M+H)cal. 491.2490 (M+H)Obs.

Workup

  1. waitAfter 15 min
  2. waitwas kept cold for 2 min.
  3. waitAfter 40 min
  4. washElution with 10% acetone in ethyl acetate

Sources & evidence

ORD record
ord-898ea60110ec472798456681912f3c36
Source dataset
uspto-grants-2008_07
Patent number
US07402606B2

Reaction notes

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