2-Amino-4-methylthiazole → tert-Butyl 4-(2-(4-methylthiazol-2-ylamino)-2-oxoethyl)piperazine-1-carboxylate

HRID 416726Notes

Reaction equation

HRID 416726 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]([OH:17])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:18][C:19]1[S:20][CH:21]=[C:22]([CH3:24])[N:23]=1.C(N(C(C)C)CC)(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>ClCCl>[CH3:24][C:22]1[N:23]=[C:19]([NH:18][C:15](=[O:17])[CH2:14][N:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]2)[S:20][CH:21]=1

Participants

6

Reactant 4

HCID 741432-Amino-4-methylthiazoleHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 27356422-{4-[(Tert-butoxy)carbonyl]piperazin-1-yl}acetic acid

Product 1

HCID 57897251tert-Butyl 4-(2-(4-methylthiazol-2-ylamino)-2-oxoethyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a round-bottomed flask containing 2-(1-tert-butoxycarbonyl-piperazin-4-yl)-acetic acid×2HCl (0.100 g, 0.36 mmol) was added 2-amino-4-methylthiazole (0.045 g, 0.39 mmol) and anhydrous dichloromethane (4 ml). The reaction mixture was cooled into an ice-bath under argon, and then diisopropylethylamine (0.139 g, 1.08 mmol) was added followed by PyBOP (0.187 g, 0.36 mmol). The ice-bath was removed and the reaction mixture was allowed to stir for 20 h under argon. The solvent was removed in vacuo, the residue was absorbed on silica gel and the free running powder was placed on a 20 g isolute silica column which was eluted with 30% ethyl acetate in dichloromethane and then 60% ethyl acetate in dichloromethane. The title compound was obtained as a gummy material (0.076 g, 62%). 1H-NMR (500 MHz, DMSO-d6) 1.39 (s, 9H, C(CH3)3), 2.25 (s, 3H, CH3), 2.45 (br s, 4H, piperazine N(CH2)2), 3.27 (s, 2H, NCH2CO), 6.76 (s, 1H, thiazole 5-H), 11.78 (s, 1H, CONH);

Workup

  1. temperatureThe reaction mixture was cooled into an ice-bath under argon
  2. customThe ice-bath was removed
  3. customThe solvent was removed in vacuo
  4. customthe residue was absorbed on silica gel
  5. washwas eluted with 30% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-883190481e2f45709696e4a3d18f52b4
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

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