2-Aminothiazole → (S)-3-Cyclohexyl-2-(4-methylsulfonyl-1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide

HRID 1018860Notes

Reaction equation

HRID 1018860 reaction equation
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH:28]1([CH2:34][C@H:35]([N:39]2[CH2:47][C:46]3[C:41](=[CH:42][CH:43]=[CH:44][C:45]=3[S:48]([CH3:51])(=[O:50])=[O:49])[C:40]2=[O:52])[C:36](O)=[O:37])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.C1(C[C@H](N2CC3C(=C(S(C)(=O)=O)C=CC=3)C2=O)C(O)=O)CCCCC1.[NH2:78][C:79]1[S:80][CH:81]=[CH:82][N:83]=1.C1(C[C@H](N2CC3C(=CC=CC=3)C2=O)C(NC2SC=CN=2)=O)CCCCC1>C(OCC)(=O)C.C(OCC)(=O)C.C(Cl)Cl>[CH:28]1([CH2:34][C@H:35]([N:39]2[CH2:47][C:46]3[C:41](=[CH:42][CH:43]=[CH:44][C:45]=3[S:48]([CH3:51])(=[O:49])=[O:50])[C:40]2=[O:52])[C:36]([NH:78][C:79]2[S:80][CH:81]=[CH:82][N:83]=2)=[O:37])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]1

Participants

8

Reactant 5

HCID 21552-AminothiazoleHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 9947513(S)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamideHCID 69695789(S)-3-cyclohexyl-2-(4-methylsulfonyl-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acidHCID 69695930(S)-3-cyclohexyl-2-(7-methylsulfonyl-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid

Product 1

HCID 10182224(S)-3-Cyclohexyl-2-(4-methylsulfonyl-1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21226138Dichloromethane ethylacetateSolvent

Procedure

BOP coupling of (S)-3-cyclohexyl-2-(4-methylsulfonyl-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid and regio-isomeric (S)-3-cyclohexyl-2-(7-methylsulfonyl-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (112 mg; 0.31 mmol) and 2-aminothiazole (54 mg; 0.52 mmol) in a manner similar to that used for the preparation of (S)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide (outlined in Example 9, Step B) provided after flash chromatography (Biotage 40M; eluent: ethyl acetate/methylene chloride: gradient 15%-50% ethyl acetate) provided 51 mg (S)-3-Cyclohexyl-2-(4-methylsulfonyl-1-oxo-1,3dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide: EI-HRMS m/e calcd for C21H25N3O4S2 (M+−2) 445.1130, found 445.1125 and 39 mg of (S)-3-Cyclohexyl-2-(7-methylsulfonyl-1-oxo-1,3dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide: EI-HRMS m/e calcd for C21H25N3O4S2 (M+) 447.1286, found 447.1280.

Sources & evidence

ORD record
ord-d9822362bdfb4bdbbf23adba6cf05afa
Source dataset
uspto-grants-2002_11
Patent number
US06482951B2

Reaction notes

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