Diisopropylethylamine → (2R,4S)-2-Hydroxy-4-((S)-3-methoxy-2-((S)-3-methoxy-2-(2-methylthiazole-5-carboxamido)propanamido)propanamido)-2-methyl-3-oxo-5-phenylpentyl 4-(trifluoromethyl)benzenesulfonate

HRID 628132Notes

Reaction equation

HRID 628132 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:8]=[CH:7][C:6]([S:9](Cl)(=[O:11])=[O:10])=[CH:5][CH:4]=1.[OH:15][C@:16]([CH3:52])([CH2:50][OH:51])[C:17](=[O:49])[C@@H:18]([NH:26][C:27](=[O:48])[C@@H:28]([NH:32][C:33](=[O:47])[C@@H:34]([NH:38][C:39]([C:41]1[S:45][C:44]([CH3:46])=[N:43][CH:42]=1)=[O:40])[CH2:35][O:36][CH3:37])[CH2:29][O:30][CH3:31])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[F:1][C:2]([F:14])([F:13])[C:3]1[CH:8]=[CH:7][C:6]([S:9]([O:51][CH2:50][C@:16]([OH:15])([CH3:52])[C:17](=[O:49])[C@@H:18]([NH:26][C:27](=[O:48])[C@@H:28]([NH:32][C:33](=[O:47])[C@@H:34]([NH:38][C:39]([C:41]2[S:45][C:44]([CH3:46])=[N:43][CH:42]=2)=[O:40])[CH2:35][O:36][CH3:37])[CH2:29][O:30][CH3:31])[CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27773994-(Trifluoromethyl)benzenesulfonyl chlorideHCID 86715357N-((S)-1-(((S)-1-(((2S,4R)-4,5-dihydroxy-4-methyl-3-oxo-1-phenylpentan-2-yl)amino)-3-methoxy-1-oxopropan-2-yl)amino)-3-methoxy-1-oxopropan-2-yl)-2-methylthiazole-5-carboxamide

Product 1

HCID 72737658(2R,4S)-2-Hydroxy-4-((S)-3-methoxy-2-((S)-3-methoxy-2-(2-methylthiazole-5-carboxamido)propanamido)propanamido)-2-methyl-3-oxo-5-phenylpentyl 4-(trifluoromethyl)benzenesulfonateYield 52%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

4-(Trifluoromethyl)benzenesulfonyl chloride (0.71 g, 2.89 mmol) in DCM (5 mL) was added dropwise to N—((S)-1-(((S)-1-(((2S,4R)-4,5-dihydroxy-4-methyl-3-oxo-1-phenylpentan-2-yl)amino)-3-methoxy-1-oxopropan-2-yl)amino)-3-methoxy-1-oxopropan-2-yl)-2-methylthiazole-5-carboxamide (1.59 g, 0.00289 mol), DMAP (0.1 g) and DIEA (0.60 mL, 3.47 mmol) in DCM (15 mL) at 0° C. The reaction was allowed to warm to room temperature and stirred overnight. The mixture was washed with 2N aqueous HCl, brine, dried (MgSO4) and evaporated. The residue was purified by Biotage flash column chromatography (5% MeOH/25% EtOAc, DCM) to give product as a white solid (1.1 g, 52%); 1H NMR (CDCl3): δ 8.08-8.03 (m, 3H), 7.82 (d, J=8.4 Hz, 2H), 7.32 (d, J=7.6 Hz, 1H), 7.28-7.15 (m, 5H), 7.02 (d, J=8.4 Hz, 1H), 6.94 (d, J=6.8 Hz, 1H), 5.40-5.32 (m, 1H), 4.76-4.72 (m, 1H), 4.58-4.52 (m, 1H), 4.30 (d, J=9.2 Hz, 1H), 3.86-3.80 (m, 3H), 3.63-3.59 (m, 1H), 3.50-3.36 (m, 7H), 3.12-3.06 (m, 1H), 2.95-2.90 (m, 1H), 2.70 (s, 3H), 0.74 (s, 3H); MS for C32H37F3N4O10S2 m/z: 759 (M+H)+.

Workup

  1. washThe mixture was washed with 2N aqueous HCl, brine
  2. dry with materialdried (MgSO4)
  3. customevaporated
  4. customThe residue was purified by Biotage flash column chromatography (5% MeOH/25% EtOAc, DCM)

Sources & evidence

ORD record
ord-664f351939ba4ea783f423a58be2cea5
Source dataset
uspto-grants-2016_04
Patent number
US09309283B2

Reaction notes

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