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

HRID 1018838Notes

Reaction equation

HRID 1018838 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](=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:40]2=[O:48])[C:36](O)=[O:37])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.[NH2:49][C:50]1[CH:55]=[CH:54][N:53]=[CH:52][N:51]=1.C1(C[C@@H](N2CC3C(=CC=CC=3)C2=O)C(NC2SC=CN=2)=O)CCCCC1>>[CH:28]1([CH2:34][CH:35]([N:39]2[CH2:47][C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:40]2=[O:48])[C:36]([NH:49][C:50]2[CH:55]=[CH:54][N:53]=[CH:52][N:51]=2)=[O:37])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]1

Participants

5

Reactant 4

HCID 689584-AminopyrimidineHCID 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 184022213-Cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-pyrimidin-4-yl-propionamideYield 74.4%

Procedure

BOP coupling of (S)-3-Cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (prepared in Example 1, Step A; 287 mg; 1.00 mmol) and 4-aminopyrimidine (108 mg; 1.14 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: 50% ethyl acetate/hexanes) 271 mg (74%)of 3-Cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-pyrimidin-4-yl-propionamide as a white foam: EI-HRMS m/e calcd for C21H24N4O2 (M+) 364.1899, found 364.1893.

Sources & evidence

ORD record
ord-4d816b43d9d9430aaa21891b4e41ac64
Source dataset
uspto-grants-2002_11
Patent number
US06482951B2

Reaction notes

Loading…