Diethylamine → (S)-3-(3-Chloro-phenyl)-2-[4-(4-isopropyl-phenyl)-thiazol-2-ylamino]-propionic acid

HRID 1162605Notes

Reaction equation

HRID 1162605 reaction equation
[NH2:1][C@@H:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([Cl:13])[CH:8]=1)[C:3]([OH:5])=[O:4].C([N:31]=[C:32]=[S:33])(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O.C(NCC)C.Br[CH2:40][C:41]([C:43]1[CH:48]=[CH:47][C:46]([CH:49]([CH3:51])[CH3:50])=[CH:45][CH:44]=1)=O.[Cl:52][C:53]1[CH:54]=[C:55]([NH:59][C:60](=[S:67])[NH:61][C@@H:62]([CH3:66])[C:63]([OH:65])=[O:64])[CH:56]=[CH:57][CH:58]=1>CO.C(Cl)Cl.CN(C=O)C>[Cl:52][C:53]1[CH:54]=[C:55]([NH:59][C:60](=[S:67])[NH:61][C@@H:62]([CH3:66])[C:63]([OH:65])=[O:64])[CH:56]=[CH:57][CH:58]=1.[Cl:13][C:9]1[CH:8]=[C:7]([CH2:6][C@H:2]([NH:1][C:32]2[S:33][CH:40]=[C:41]([C:43]3[CH:48]=[CH:47][C:46]([CH:49]([CH3:51])[CH3:50])=[CH:45][CH:44]=3)[N:31]=2)[C:3]([OH:5])=[O:4])[CH:12]=[CH:11][CH:10]=1

Participants

10

Reactant 5

HCID 8021DiethylamineHCID 27614923-chloro-L-phenylalanineHCID 4154759Fmoc isothiocyanateHCID 140427562-Bromo-1-(4-(propan-2-yl)phenyl)ethan-1-oneHCID 86601766(S)-3-(3-Chloro-phenyl)-2-thioureido-propionic acid

Product 2

HCID 59520374(S)-3-(3-Chloro-phenyl)-2-[4-(4-isopropyl-phenyl)-thiazol-2-ylamino]-propionic acidHCID 86601766(S)-3-(3-Chloro-phenyl)-2-thioureido-propionic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

(S)-3-(3-Chloro-phenyl)-2-thioureido-propionic acid was prepared following general procedure D using (S)-2-amino-3-(3-chloro-phenyl)-propionic acid (399 mg, 2 mmol), Fmoc isothiocyanate (590 mg, 2 mmol) and DMF (6 mL). The residue was combined with DCM (8 mL) and diethyl amine (2 mL). LCMS m/z: 259 (M+1)+. (S)-3-(3-Chloro-phenyl)-2-[4-(4-isopropyl-phenyl)-thiazol-2-ylamino]-propionic acid was prepared following general procedure B using 2-bromo-1-(4-isopropyl-phenyl)-ethanone (2 mmol), (S)-3-(3-chloro-phenyl)-2-thioureido-propionic acid and MeOH (10 mL). Purification by flash chromatography (ethyl acetate/hexanes 1:2, 1:1, with 0.5% v/v acetic acid) gave the product (545 mg). LCMS m/z: 401 (M+1)+; 1H-NMR (400 MHz, CDCl3): 7.39-7.45 (m, 3H), 7.18-7.25 (m, 5H), 6.37 (s, 1H), 4.15 (t, 1H), 3.38 (dd, 1H), 3.26 (dd, 1H), 2.92 (sept, 1H), 1.27 (d, 6H).

Workup

  1. customPurification by flash chromatography (ethyl acetate/hexanes 1:2, 1:1

Sources & evidence

ORD record
ord-2f4a276cdfba402b899bf7369e6d6a18
Source dataset
uspto-grants-2010_10
Patent number
US07820704B2

Reaction notes

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