2-Amino-5-chlorothiazole hydrochloride → HCID 10204182, compound

HRID 1018835Notes

Reaction equation

HRID 1018835 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]=[C:44]([N+:48]([O-:50])=[O:49])[CH:45]=3)[C:40]2=[O:51])[C:36](O)=[O:37])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.Cl.[NH2:53][C:54]1[S:55][C:56]([Cl:59])=[CH:57][N:58]=1.C1(C[C@H](N2CC3C(=CC=CC=3)C2=O)C(NC2SC=CN=2)=O)CCCCC1>>[Cl:59][C:56]1[S:55][C:54]([NH:53][C:36](=[O:37])[C@@H:35]([N:39]2[CH2:47][C:46]3[C:41](=[CH:42][CH:43]=[C:44]([N+:48]([O-:50])=[O:49])[CH:45]=3)[C:40]2=[O:51])[CH2:34][CH:28]2[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]2)=[N:58][CH:57]=1

Participants

5

Reactant 4

HCID 1487432-Amino-5-chlorothiazole hydrochlorideHCID 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 69696537HCID 69696537, compound

Product 1

HCID 10204182HCID 10204182, compoundYield 32.4%

Procedure

BOP coupling of ((S)-3-cyclohexyl-2-(5-nitro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (ca. 1:1 mixture of 5,6-regioisomers, prepared in Step C; 307 mg; 0.92 mmol) and 2-amino-5-chlorothiazole hydrochloride (360 mg; 2.04 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 chromatography, (Biotage 40M, eluent: 25% ethyl acetate/hexanes) 134 mg of (S)- N-(5-Chloro-thiazol-2-yl)-3-cyclohexyl-2-(5-nitro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide: EI-HRMS m/e calcd for C20H21ClN4O4S (M+) 448.0972, found 448.0970 and 111 mg of regioisomeric (S)-N-(5-Chloro-thiazol-2-yl)-3-cyclohexyl-2-(6-nitro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide: EI-HRMS m/e calcd for C20H21ClN4O4S (M+) 448.0972, found 448.0972.

Sources & evidence

ORD record
ord-18e2a289a6bb4f9092831f924a6f717f
Source dataset
uspto-grants-2002_11
Patent number
US06482951B2

Reaction notes

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