N-(tert-Butoxycarbonyl)-4-chloro-L-phenylalanine → (S)-tert-Butyl 4-(4-chlorobenzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide

HRID 598878Notes

Reaction equation

HRID 598878 reaction equation
FC(F)(F)[C:3]1[CH:23]=[CH:22][C:6]([CH2:7][C@H:8]2[CH2:12][O:11][S:10](=[O:14])(=[O:13])[N:9]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[CH:5][CH:4]=1.C(OC(N[C@@H](CC1C=CC([Cl:45])=CC=1)C(O)=O)=O)(C)(C)C.C(OC(N[C@@H](CC1C=CC(C(F)(F)F)=CC=1)C(O)=O)=O)(C)(C)C>>[Cl:45][C:3]1[CH:23]=[CH:22][C:6]([CH2:7][C@H:8]2[CH2:12][O:11][S:10](=[O:14])(=[O:13])[N:9]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[CH:5][CH:4]=1

Participants

4

Reactant 3

HCID 2734499N-(tert-Butoxycarbonyl)-4-chloro-L-phenylalanineHCID 7021025N-((1,1-Dimethylethoxy)carbonyl)-4-(trifluoromethyl)-L-phenylalanineHCID 57634052tert-Butyl (4S)-4-(4-(trifluoromethyl)benzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide

Product 1

HCID 86635689(S)-tert-Butyl 4-(4-chlorobenzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide

Procedure

A 60% dispersion of sodium hydride in mineral oil (9.6 mg, 251 μmol) was added to a mixture of 1-(isoquinolin-6-yl)-1H-pyrazol-4-amine (44 mg, 209 μmol) and (S)-tert-butyl 4-(4-chlorobenzyl)-1,2,3-oxathiazolidine-3-carboxylate-2,2-dioxide (109 mg, 314 μmol) in DMF (1 mL) at ambient temperature and the mixture was stirred at ambient temperature for 1.5 hours. H2O (15 mL) was added, and the mixture was extracted with DCM (4×15 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The resulting yellow solid was dissolved in DCM (3 mL), TFA (2 mL) was added, and the mixture was stirred at ambient temperature for 2 hours. Toluene (3 mL) was added, and the mixture was concentrated under reduced pressure. The resulting orange oil was dissolved in DCM, evaporated onto a silica gel plug, and purified by flash chromatography (Biotage Si 25+M, 5% to 10% 2 N NH3 in MeOH/DCM) to provide N-((S)-2-amino-3-(4-chlorophenyl)propyl)-1-(isoquinolin-6-yl)-1H-pyrazol-4-amine (18 mg, 23% yield) as an off-white solid. LCMS (API-ES) m/z (%): 412.2 (100%, M++H); 1H NMR (300 MHz, CDCl3) δ ppm 1.54 (br s, 3H), 2.62 (dd, J=13.1, 8.1 Hz, 1H), 2.79-2.94 (m, 2H), 3.15 (dd, J=11.8, 2.6 Hz, 1H), 3.25 (d, J=4.1 Hz, 1H), 7.17 (d, J=7.8 Hz, 2H), 7.31 (d, J=7.8 Hz, 2H) 7.45 (s, 2H), 7.64 (d, J=5.5 Hz, 1H), 7.89 (s, 1H), 8.00 (s, 2H), 8.51 (d, J=5.5 Hz, 1H), 9.20 (s, 1H). (S)-tert-Butyl 4-(4-chlorobenzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide was prepared in a similar manner as that described for (S)-tert-butyl 4-(4-(trifluoromethyl)benzyl)-1,2,3-oxathiazolidine-3-carboxylate-2,2-dioxide in Scheme 1, using (S)-2-(tert-butoxycarbonylamino)-3-(4-chlorophenyl)propanoic acid (commercially available from 3B Scientific Corporation Product List (Order Number 3B3-011434)) instead of (S)-2-(tert-butoxycarbonylamino)-3-(4-(trifluoromethyl)phenyl)propanoic acid.

Sources & evidence

ORD record
ord-575cb1aab6fc42e09279fe9f52c4ee81
Source dataset
uspto-grants-2011_03
Patent number
US07897619B2

Reaction notes

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