Aminopyrazine → 3-Cycloheptyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide

HRID 1018861Notes

Reaction equation

HRID 1018861 reaction equation
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=C[C:11]=2N=N1.C1(C[C@H](N2CC3C(=CC=CC=3S(C)(=O)=O)C2=O)C(O)=O)CCCCC1.C1(C[C@H](N2CC3C(=C(S(C)(=O)=O)C=CC=3)C2=O)C(O)=O)CCCCC1.NC1C=NC=CN=1.[CH:85]1([CH2:91][C@H:92]([N:101]2[CH2:109][C:108]3[C:103](=[CH:104][CH:105]=[CH:106][CH:107]=3)[C:102]2=[O:110])[C:93]([NH:95][C:96]2[S:97][CH:98]=[CH:99][N:100]=2)=[O:94])[CH2:90][CH2:89][CH2:88][CH2:87][CH2:86]1>C(OCC)(=O)C.C(Cl)Cl>[CH:85]1([CH2:91][CH:92]([N:101]2[CH2:109][C:108]3[C:103](=[CH:104][CH:105]=[CH:106][CH:107]=3)[C:102]2=[O:110])[C:93]([NH:95][C:96]2[S:97][CH:98]=[CH:99][N:100]=2)=[O:94])[CH2:86][CH2:87][CH2:88][CH2:89][CH2:90][CH2:11]1

Participants

7

Reactant 5

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 69695789(S)-3-cyclohexyl-2-(4-methylsulfonyl-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acidHCID 69695930(S)-3-cyclohexyl-2-(7-methylsulfonyl-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid

Product 1

HCID 102713163-Cycloheptyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide

Reagents, catalysts & solvents 1

HCID 21226138Dichloromethane ethylacetateSolvent

Procedure

BOP coupling of (S)-3-cyclohexyl-2-(4-methylsulfonyl-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid and regio-isomeric (S)-3-cyclohexyl-2-(7-methylsulfonyl-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (200 mg; 0.55 mmol) and 2-aminopyrazine (88 mg; 0.91 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 40S; eluent: ethyl acetate/methylene chloride, gradient:20% to 60%) a crude mixture that was further purified by reverse phase HPLC (Rainin Dynamax SD-1 instrument) using a gradient of 10% acetonitrile/water/0.1% trifluoroacetic acid to 90% acetonitrile on a C18 column to give 21 mg of (S)-3-Cyclohexyl-2-(4-methylsulfonyl-1-oxo-1,3-dihydro-isoindol-2-yl)-N-pyrazin-2-yl-propionamide: EI-HRMS m/e calcd for C22H24N4O4SNa (M++Na+) 465.1567, found 465.1570 and 13 mg of (S)-3-Cyclohexyl-2-(7-methylsulfonyl-1-oxo-1,3-dihydro-isoindol-2-yl)-N-pyrazin-2-yl-propionamide: EI-HRMS m/e calcd for C22H24N4O4SNa (M++Na+) 465.1567, found 465.1568.

Sources & evidence

ORD record
ord-af5a527a6c1d40839aca57c242aa96ba
Source dataset
uspto-grants-2002_11
Patent number
US06482951B2

Reaction notes

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