Dimethyl Sulfoxide → {1-[(4-phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methyl (1S)-1-(oxo{[(1R)-1-phenylethyl]amino}acetyl)pentylcarbamate

HRID 1180770Notes

Reaction equation

HRID 1180770 reaction equation
[OH:1][CH:2]([C@@H:14]([NH:19][C:20](=[O:39])[O:21][CH2:22][C:23]1([CH2:27][C:28]2[S:29][CH:30]=[C:31]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[N:32]=2)[CH2:26][CH2:25][CH2:24]1)[CH2:15][CH2:16][CH2:17][CH3:18])[C:3](=[O:13])[NH:4][C@@H:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:6].C(Cl)(=O)C(Cl)=O.CS(C)=O.C(N(CC)CC)C>ClCCl.C(OCC)(=O)C.CCCCCC>[O:13]=[C:3]([NH:4][C@@H:5]([C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)[CH3:6])[C:2]([C@@H:14]([NH:19][C:20](=[O:39])[O:21][CH2:22][C:23]1([CH2:27][C:28]2[S:29][CH:30]=[C:31]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[N:32]=2)[CH2:26][CH2:25][CH2:24]1)[CH2:15][CH2:16][CH2:17][CH3:18])=[O:1]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 11753176{1-[(4-phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate

Product 1

HCID 11295769{1-[(4-phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methyl (1S)-1-(oxo{[(1R)-1-phenylethyl]amino}acetyl)pentylcarbamateYield 96%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a solution of 0.2 g (0.364 mmol) of {1-[(4-phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate in 3 mL of dichloromethane cooled to −60° C. was added 0.079 mL (0.91 mmol) of oxalyl chloride and—0.129 mL (1.82 mmol) od dimethylsulfoxide, followed by the addition of 0.204 mL (1.45 mmol) of triethylamine. After stirring for 15 min, the reaction was warmed to room temperature and applied directly to a silica gel column using ethyl acetate:hexane (3:7) as the eluent to afford 0.19 g (96%) of {1-[(4-phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methyl (1S)-1-(oxo{[(1R)-1-phenylethyl]amino}acetyl)pentylcarbamate as a colorless oil. 1H NMR (300 MHz, DMSO-d6) δ 9.21 (d, J=8 Hz, 1H), 7.98 (m, 3H), 7.64 (d, J=8 Hz, 1H), 7.25-7.23 (m, 8 H), 4.96-5.01 (m, 1H), 4.80 (m, 1H), 4.01 (s, 2H), 3.30 (s, 2H), 2.12-1.64 (m, 10 H), 1.42 (d, J=7 Hz, 3H), 1.29-1.21 (m, 2H), 0.82 (t, J=7 Hz, 3H). LC-MS m/z 548 (M+H).

Sources & evidence

ORD record
ord-96918f06e4e54dd782e783b0ffd712ee
Source dataset
uspto-grants-2007_10
Patent number
US07282512B2

Reaction notes

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