Benzylamine → 2-(Tert-butoxycarbonylamino)-4-methylthiazole-5-carboxylic acid benzylamide

HRID 45396Notes

Reaction equation

HRID 45396 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[S:10][C:11]([C:15]([OH:17])=O)=[C:12]([CH3:14])[N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(NC(C)C)(C)C.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[CH2:47]([NH2:54])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>ClCCl.C(OCC)(=O)C>[CH2:47]([NH:54][C:15]([C:11]1[S:10][C:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[N:13][C:12]=1[CH3:14])=[O:17])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1

Participants

8

Reactant 5

HCID 7504BenzylamineHCID 7912DiisopropylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2756770N-Boc-amino-4-methylthiazole-5-carboxylic acid

Product 1

HCID 866425212-(Tert-butoxycarbonylamino)-4-methylthiazole-5-carboxylic acid benzylamideYield 50.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 2-(tert-butoxycarbonylamino)-4-methylthiazole-5-carboxylic acid (2.97 g, 11.50 mmol) and diisopropylamine (8.5 mL, 48.70 mmol) in dichloromethane (40 mL) was added N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.25 g, 11.50 mmol) and 1-hydroxybenzotriazole (2.02 g, 14.80 mmol). After 30 min benzylamine (1.7 mL, 15.60 mmol) was added. The resultant mixture was stirred at ambient temperature over 8 h, diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash column chromatography eluting with ethyl acetate/hexanes (5/95 to 100/0) to afford 2-(tert-butoxycarbonylamino)-4-methylthiazole-5-carboxylic acid benzylamide (2.00 g, 50% yield).

Workup

  1. washwashed with water and brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash column chromatography
  6. washeluting with ethyl acetate/hexanes (5/95 to 100/0)

Sources & evidence

ORD record
ord-a0ca25b0155045efa99fa0e55e339a4f
Source dataset
uspto-grants-2013_09
Patent number
US08541457B2

Reaction notes

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