2-Aminothiazole → HCID 10200227, compound

HRID 1018856Notes

Reaction equation

HRID 1018856 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.C1(C[C@H](N2CC3C(=C([F:48])C=CC=3)C2=O)C(O)=O)CCCCC1.NC1SC=CN=1.[CH:56]1([CH2:62][C@H:63]([N:72]2[CH2:80][C:79]3[C:74](=[CH:75][CH:76]=[CH:77][CH:78]=3)[C:73]2=[O:81])[C:64]([NH:66][C:67]2[S:68][CH:69]=[CH:70][N:71]=2)=[O:65])[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]1>>[CH:56]1([CH2:62][C@H:63]([N:72]2[CH2:80][C:79]3[C:74](=[CH:75][CH:76]=[CH:77][C:78]=3[F:48])[C:73]2=[O:81])[C:64]([NH:66][C:67]2[S:68][CH:69]=[CH:70][N:71]=2)=[O:65])[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]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 69694866HCID 69694866, compound

Product 1

HCID 10200227HCID 10200227, compoundYield 30%

Procedure

BOP coupling of (S)-3-cyclohexyl-2-(4-fluoro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic and (S)-3-cyclohexyl-2-(7-fluoro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (499 mg; 1.63 mmol, as a 1:1 mixture of regioisomers) and 2-aminothiazole (376 mg; 3.64 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: 30% ethyl acetate/hexanes) (S)-3-Cyclohexyl-2-(4-fluoro-1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide (221 mg): EI-HRMS calcd for C20H22FN3O2S (M+) 387.1417, found 387.1422; and impure (S)-3-Cyclohexyl-2-(7-fluoro-1-oxo-1,3dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide which was further purified by radial chromatography (eluent:35% ethyl acetate/hexanes) providing 48 mg of pure (S)-3-Cyclohexyl-2-(7-fluoro-1-oxo-1,3dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamideas a white foam: EI-HRMS m/e calcd for C20H22FN3O2S (M+) 387.1417, found 387.1415.

Sources & evidence

ORD record
ord-9d10f3369a324b19b3abd2c868a0e3a7
Source dataset
uspto-grants-2002_11
Patent number
US06482951B2

Reaction notes

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