Aminopyrazine → HCID 10200227, compound

HRID 1018858Notes

Reaction equation

HRID 1018858 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](=[C:42]([F:48])[CH:43]=[CH:44][CH:45]=3)[C:40]2=[O:49])[C:36]([OH:38])=O)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.NC1C=NC=CN=1.[CH:57]1([CH2:63][C@H:64]([N:73]2[CH2:81][C:80]3[C:75](=[CH:76][CH:77]=[CH:78][CH:79]=3)[C:74]2=[O:82])[C:65]([NH:67][C:68]2[S:69][CH:70]=[CH:71][N:72]=2)=[O:66])[CH2:62][CH2:61][CH2:60][CH2:59][CH2:58]1>>[CH:57]1([CH2:63][C@H:64]([N:73]2[CH2:81][C:80]3[C:75](=[CH:76][CH:77]=[CH:78][C:79]=3[F:48])[C:74]2=[O:82])[C:65]([NH:67][C:68]2[S:69][CH:70]=[CH:71][N:72]=2)=[O:66])[CH2:62][CH2:61][CH2:60][CH2:59][CH2:58]1.[CH:28]1([CH2:34][C@H:35]([N:39]2[CH2:47][C:46]3[C:41](=[C:42]([F:48])[CH:43]=[CH:44][CH:45]=3)[C:40]2=[O:49])[C:36]([NH:67][C:68]2[S:69][CH:70]=[CH:71][N:72]=2)=[O:38])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]1

Participants

6

Reactant 4

HCID 78747AminopyrazineHCID 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 2

HCID 10200227HCID 10200227, compoundYield 30%HCID 10200228HCID 10200228, compound

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 (331 mg; 1.08 mmol, as a 1:1 mixture of regioisomers) and 2-aminopyrazine (232 mg; 2.41 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 and (S)-3-Cyclohexyl-2-(7-fluoro-1-oxo-1,3 dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide which were further purified by reverse phase HPLC (Rainin Dynamax SD-1 instrument) using a gradient of 40% acetonitrile/water/0.1% trifluoroacetic acid to 100% acetonitrile on a C18 column to provide 39 mg of pure (S)-3-Cyclohexyl-2-(7-fluoro-1-oxo-1,3dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide as a white foam: EI-HRMS m/e calcd for C21H23FN4O2 (M+) 382.1805, found 382.1794 and 43 mg of regioisomer (S)-3-Cyclohexyl-2-(7-fluoro-1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide: EI-HRMS m/e calcd for C21H23FN4O2 (M+) 382.1805, found 382.1810.

Sources & evidence

ORD record
ord-7c43234070404053a9f42385174b2343
Source dataset
uspto-grants-2002_11
Patent number
US06482951B2

Reaction notes

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