2-Aminothiazole → HCID 10135824, compound

HRID 1018868Notes

Reaction equation

HRID 1018868 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[Cl:48])[C:40]2=[O:49])[C:36]([OH:38])=O)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.[NH2:50][C:51]1[S:52][CH:53]=[CH:54][N:55]=1.C1(C[C@H](N2CC3C(=CC=CC=3)C2=O)C(NC2SC=CN=2)=O)CCCCC1>>[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[Cl:48])[C:40]2=[O:49])[C:36]([NH:50][C:51]2[S:52][CH:53]=[CH:54][N:55]=2)=[O:38])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1

Participants

5

Reactant 4

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 69694579HCID 69694579, compound

Product 1

HCID 10135824HCID 10135824, compoundYield 32.7%

Procedure

BOP coupling of (S)-3-cyclohexyl-2-(4-Chloro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (ca. 1:1 mixture of regioisomers, prepared in Step C; 326 mg; 1.0 mmol) and 2-aminothiazole (231 mg; 2.23 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 as outlined in Example 9, Step B) provided after chromatography (Biotage 40M column, eluent: 5% to 30% gradient of ethyl acetate/hexanes) 132 mg of (S)-3-Cyclohexyl-2-(4-Chloro-1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide: EI-HRMS m/e calcd for C20H22ClN3O2S (M++Na+) 426.1013, found 426.1016; and 91 mg of regioisomeric (S)-3-Cyclohexyl-2-(7-Chloro-1-oxo-1,3dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide: EI-HRMS m/e calcd for C20H22ClN3O2SNa (M++Na+) 426.1013, found 426.1017.

Sources & evidence

ORD record
ord-ee4703a50fe34bdca0679e0a604a4dd5
Source dataset
uspto-grants-2002_11
Patent number
US06482951B2

Reaction notes

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