2-Aminothiazole → HCID 57657323, compound

HRID 1920762Notes

Reaction equation

HRID 1920762 reaction equation
[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:2]([C:10]([OH:12])=O)[CH2:3][CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[S:56]1[CH:60]=[CH:59][N:58]=[C:57]1[NH2:61]>CN(C=O)C.O>[C:16]([O:15][C:13](=[O:14])[NH:1][C@H:2]([C:10](=[O:12])[NH:61][C:57]1[S:56][CH:60]=[CH:59][N:58]=1)[CH2:3][CH:4]1[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]1)([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 4

HCID 21552-AminothiazoleHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 10588189(2S)-2-(((tert-butoxy)carbonyl)amino)-3-cyclohexylpropanoic acid

Product 1

HCID 57657323HCID 57657323, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of Boc-Cha-OH (9.2 g, 34 mmol), DIEA (15 ml, 85 mmol) and BOP (16.5 g, 37 mmol) in DMF (80 ml) was maintained at ambient temperature for 40 minutes followed by the addition of thiazol-2-ylamine (3.4 g, 34 mmol). Reaction was maintained at ambient temperature for 2 hours. Reaction mixture was diluted with water (200 ml) and extracted with EtOAc (2×150 ml). Organic layer was washed with brine (100 ml), dried over anh. MgSO4 and evaporated in vacuum. Residue was subjected to flash chromatography on CombiFlash® Companion unit equipped with RediSep® flash column (normal phase, 35-60 micron average particle size silicagel, 40 g, Teledyne Isco); flow rate=35 ml/min; injection volume 2 ml; mobile phase A: hexane; mobile phase B: EtOAc; gradient 0-70% B in 1 h. Fractions containing the desired product were combined and concentrated in vacuum to provide target compound (8.89 g, 74%) as yellow oil. LC-MS [M+H] 354.4 (C17H27N3O3S+H, requires 354.49).

Workup

  1. customReaction
  2. customReaction mixture
  3. extractionextracted with EtOAc (2×150 ml)
  4. washOrganic layer was washed with brine (100 ml)
  5. dry with materialdried over anh. MgSO4
  6. customevaporated in vacuum
  7. customequipped with RediSep® flash column (normal phase, 35-60 micron average particle size silicagel, 40 g, Teledyne Isco)
  8. additionFractions containing the desired product
  9. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-c6c53b41bdc0430ba15d7a9ed36e22aa
Source dataset
uspto-grants-2012_05
Patent number
US08173645B2

Reaction notes

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