2-Aminothiazole → (R)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide

HRID 1018831Notes

Reaction equation

HRID 1018831 reaction equation
[CH:1]1([CH2:7][C@@H:8]([N:12]2[CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]2=[O:21])[C:9]([OH:11])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.F[P-](F)(F)(F)(F)F.CN(C)C(O)=[N+](C)C.[NH2:37][C:38]1[S:39][CH:40]=[CH:41][N:42]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[CH:1]1([CH2:7][C@@H:8]([N:12]2[CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]2=[O:21])[C:9]([NH:37][C:38]2[S:39][CH:40]=[CH:41][N:42]=2)=[O:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 81531DiisopropylethylamineHCID 1477120(R)-3-Cyclohexyl-2-(1-oxoisoindolin-2-yl)propanoic acidHCID 21864398Tetramethyluronium hexafluorophosphate

Product 1

HCID 10133709(R)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamideYield 81.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (R)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (prepared in Step A, 144 mg; 0.5 mmol), O-benzotriazol-1-yl-N,N,N′,N′, -tetramethyluronium hexafluorophosphate (BOP, 268 mg; 0.55 mmol) and 2-aminothiazole (50 mg; 0.5 mmol) in dry methylene chloride (3 mL) at room temperature was added N,N-diisopropylethylamine (0.20 mL; 1.15 mmol) dropwise. The mixture was allowed to stir for 1 h. The mixture was then diluted with methylene chloride and washed with water. The organic layer was dried (Na2SO4), filtered and concentrated in vacuo to give a crude residue. Flash chromatography (Merck Silica gel 60, 230-400 mesh, eluent: 30% ethyl acetate/hexanes) provided 150 mg (81%) of (R)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide as an off white foam: EI-HRMS m/e calcd for C20H23N3O2S (M+) 369.1511, found 369.1511.

Workup

  1. washwashed with water
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give a crude residue

Sources & evidence

ORD record
ord-05a0e2e611ee4a0b90a2a9fe63ee121f
Source dataset
uspto-grants-2002_11
Patent number
US06482951B2

Reaction notes

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