2-Amino-5-chlorothiazole hydrochloride → N-(5-Chloro-thiazol-2-yl)-3-cyclopentyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide

HRID 1018843Notes

Reaction equation

HRID 1018843 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][CH:45]=3)[C:40]2=[O:48])[C:36](O)=[O:37])[CH2:33][CH2:32]C[CH2:30][CH2:29]1.Cl.[NH2:50][C:51]1[S:52][C:53]([Cl:56])=[CH:54][N:55]=1.C1(C[C@H](N2CC3C(=CC=CC=3)C2=O)C(NC2SC=CN=2)=O)CCCCC1>>[Cl:56][C:53]1[S:52][C:51]([NH:50][C:36](=[O:37])[CH:35]([N:39]2[CH2:47][C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:40]2=[O:48])[CH2:34][CH:28]2[CH2:29][CH2:30][CH2:32][CH2:33]2)=[N:55][CH:54]=1

Participants

5

Reactant 4

HCID 1487432-Amino-5-chlorothiazole hydrochlorideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 1477119(S)-3-Cyclohexyl-2-(1-oxoisoindolin-2-yl)propanoic acidHCID 9947513(S)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide

Product 1

HCID 10200378N-(5-Chloro-thiazol-2-yl)-3-cyclopentyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamideYield 74.4%

Procedure

BOP coupling of 3-Cyclopentyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (prepared in Example 1, Step A; 277 mg; 1.0 mmol) and 2-amino-5-chlorothiazole hydrochloride (397 mg; 2.30 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 1, Step B) provided after Flash chromatography (Biotage 40M eluent: 20% ethyl acetate/hexanes) 290 mg (74%) of N-(5-Chloro-thiazol-2-yl)-3-cyclopentyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide as a light yellow solid: EI-HRMS m/e calcd for C19H21N3O2S (M+) 389.0965, found 389.0966.

Sources & evidence

ORD record
ord-7f44a336bded4089b0b51b1325ceec09
Source dataset
uspto-grants-2002_11
Patent number
US06482951B2

Reaction notes

Loading…