Diisopropylethylamine → Tert-butyl 5-(methylcarbamoyl)thiazol-2-ylcarbamate

HRID 1874007Notes

Reaction equation

HRID 1874007 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[S:10][C:11]([C:14]([OH:16])=O)=[CH:12][N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.O[N:19]1[C:23]2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN>C(#N)C>[CH3:23][NH:19][C:14]([C:11]1[S:10][C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[N:13][CH:12]=1)=[O:16]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 6364545Methylamine hydrochlorideHCID 222714422-N-Boc-Amino-Thiazole-5-Carboxylic Acid

Product 1

HCID 86649520Tert-butyl 5-(methylcarbamoyl)thiazol-2-ylcarbamateYield 73%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a heterogeneous mixture of 2-(tert-butoxycarbonylamino)thiazole-5-carboxylic acid (1.0 g, 4.1 mmol), 1-hydroxybenzotriazole hydrate (0.63 g, 4.1 mmol), N,N-diisopropylethylamine (4.3 mL, 24 mmol), methylamine hydrochloride (0.83 g, 12 mmol) in anhydrous acetonitrile (20 mL), was added WSCDI (2.4 g, 12 mmol) at room temperature under a nitrogen atmosphere and stirred at room temperature overnight. The reaction mixture was concentrated in vacuo. To the residue was added saturated aqueous sodium bicarbonate solution (20 mL), ethyl acetate (6 mL), and heptane (2 mL). The solid that separates out was filtered, washed with water (2×2 mL) and diethyl ether (2×4 mL), and dried to give tert-butyl 5-(methylcarbamoyl)thiazol-2-ylcarbamate (0.77 g, 73% yield) as a white solid. MS found: (M+H)+=258; 1H NMR (400 MHz, methanol-d4) δ ppm 7.83 (s, 1H), 2.87 (s, 3H), 1.55 (s, 9H).

Workup

  1. additionwas added WSCDI (2.4 g, 12 mmol) at room temperature under a nitrogen atmosphere
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. additionTo the residue was added saturated aqueous sodium bicarbonate solution (20 mL), ethyl acetate (6 mL), and heptane (2 mL)
  4. filtrationThe solid that separates out was filtered
  5. washwashed with water (2×2 mL) and diethyl ether (2×4 mL)
  6. customdried

Sources & evidence

ORD record
ord-4b75c05436cc4bc0a166d7589795cc22
Source dataset
uspto-grants-2012_11
Patent number
US08304539B2

Reaction notes

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