2-Amino-5-bromopyridine → (S)-N-(5-Bromo-pyridin-2-yl)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide

HRID 1018855Notes

Reaction equation

HRID 1018855 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]([OH:38])=O)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.[NH2:49][C:50]1[CH:55]=[CH:54][C:53]([Br:56])=[CH:52][N:51]=1.C1(C[C@@H](N2CC3C(=CC=CC=3)C2=O)C(NC2SC=CN=2)=O)CCCCC1>>[Br:56][C:53]1[CH:54]=[CH:55][C:50]([NH:49][C:36](=[O:38])[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])[CH2:34][CH:28]2[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]2)=[N:51][CH:52]=1

Participants

5

Reactant 4

HCID 706222-Amino-5-bromopyridineHCID 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 59898549(S)-N-(5-Bromo-pyridin-2-yl)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamideYield 54.9%

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 2-amino-5-bromopyridine (173 mg; 1.00 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: 30% ethyl acetate/hexanes) 243 mg (55%)of (S)-N-(5-Bromo-pyridin-2-yl)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide as a white foam: EI-HRMS m/e calcd for C22H24BrN3O2 (M+) 441.1052, found 441.1036.

Sources & evidence

ORD record
ord-1a75334dfd434cbab2997f1af7aef026
Source dataset
uspto-grants-2002_11
Patent number
US06482951B2

Reaction notes

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