2-Amino-4-methylpyrimidine → (S)-3-Cyclohexyl-N-(2-methyl-pyrimidin-4-yl)-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide

HRID 1018859Notes

Reaction equation

HRID 1018859 reaction equation
F[P-](F)(F)(F)(F)F.[N:8]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:12]2C=CC=C[C:11]=2N=N1.C1(C[C@H](N2CC3C(=CC=CC=3)C2=O)C(O)=O)CCCCC1.NC1N=CC=C(C)N=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]2S[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][CH:79]=3)[C:74]2=[O:82])[C:65]([NH:67][C:68]2[CH:11]=[CH:12][N:8]=[C:71]([CH3:70])[N:72]=2)=[O:66])[CH2:62][CH2:61][CH2:60][CH2:59][CH2:58]1

Participants

5

Reactant 4

HCID 79392-Amino-4-methylpyrimidineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 1477119(S)-3-Cyclohexyl-2-(1-oxoisoindolin-2-yl)propanoic acidHCID 10133709(R)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide

Product 1

HCID 59898551(S)-3-Cyclohexyl-N-(2-methyl-pyrimidin-4-yl)-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamideYield 65%

Procedure

BOP coupling of (S)-3-Cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (prepared in Example 1, Step A; 150 mg; 0.52 mmol) and 2-amino-6-methylpyrimidine (57 mg; 0.52 mmol) in a manner similar to that used for the preparation of (R)-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 (Merck Silica gel 60, 230-400 mesh, eluent: 65% ethyl acetate/hexanes) 109 mg of (S)-3-Cyclohexyl-N-(2-methyl-pyrimidin-4-yl)-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide as a white foam: EI-HRMS m/e calcd for C22H26N4O2 (M+) 378.2056, found 378.2054.

Sources & evidence

ORD record
ord-07e3c82f1bc94f23b44b7e47b606bc41
Source dataset
uspto-grants-2002_11
Patent number
US06482951B2

Reaction notes

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