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

HRID 1018862Notes

Reaction equation

HRID 1018862 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=CN=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(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

8

Reactant 5

HCID 689584-AminopyrimidineHCID 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 2

HCID 8857Ethyl AcetateSolventHCID 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 4-aminopyrimidine (89 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: 25% to 70% ethyl acetate) to give 83 mg of (S)-3-Cyclohexyl-2-(4-methylsulfonyl-1-oxo-1,3-dihydro-isoindol-2-yl)-N-pyrimidin-4-yl-propionamide as a foam: EI-HRMS m/e calcd for C22H24N4O4SNa (M++Na+) 465.1567, found 465.1568 and 77 mg (S)-3-Cyclohexyl-2-(7-methylsulfonyl-1-oxo-1,3-dihydro-isoindol-2-yl)-N-pyrimidin-4-yl-propionamide as a foam: EI-HRMS m/e calcd for C22H26N4O4SNa (M++Na+) 465.1567, found 465.1572.

Sources & evidence

ORD record
ord-7fdf0069532b48d1a5fa9f419e4ec8a4
Source dataset
uspto-grants-2002_11
Patent number
US06482951B2

Reaction notes

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