Ammonia → 2-(1H-Imidazol-2-yl)-1,3-thiazole

HRID 44817Notes

Reaction equation

HRID 44817 reaction equation
[Li]CCCC.CO[CH:8](OC)[CH2:9][NH2:10].[S:13]1[CH:17]=[CH:16][N:15]=[C:14]1[C:18]#[N:19].N>CCCCCC.C1COCC1>[NH:10]1[CH:9]=[CH:8][N:19]=[C:18]1[C:14]1[S:13][CH:17]=[CH:16][N:15]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 89728Aminoacetaldehyde dimethyl acetalHCID 151114801,3-Thiazole-2-carbonitrileHCID 178418339Butyllithium

Product 1

HCID 222603952-(1H-Imidazol-2-yl)-1,3-thiazole

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

A 2.5 M solution of nBuLi (2.0 eq) in hexane was added under argon to a solution of 2,2-dimethoxyethanamine (2.0 eq) in THF at −78° C. After stirring for 30 min, thiazole-2-carbonitrile (2-Im-2, 3.0 g, 1.0 eq) was added and the resulting solution was stirred at 0° C. for 2 h, then quenched with 20 mL of 5% MeOH in water. The volatiles were removed and 6N HCl was added to adjust to pH=1. The acidic solution was refluxed overnight, cooled to rt then poured into a mixture of ice and aqueous Na2CO3. This was extracted with EtOAc and the organic layer was concentrated to give Imadazole 2. LCMS (0.01% Ammonia): 152.1 m/z (M+H)+; 1H-NMR (DMSO-d6, 500 MHz): δ: 13.19 (bs, 1H), 7.98 (d, 1H, J=3.0 Hz), 7.82 (d, 1H, J=3.0 Hz), 7.36 (s, 1H), 7.14 (s, 1H).

Workup

  1. stirringthe resulting solution was stirred at 0° C. for 2 h
  2. customquenched with 20 mL of 5% MeOH in water
  3. customThe volatiles were removed
  4. addition6N HCl was added
  5. temperatureThe acidic solution was refluxed overnight
  6. additionthen poured into a mixture of ice and aqueous Na2CO3
  7. extractionThis was extracted with EtOAc
  8. concentrationthe organic layer was concentrated
  9. customto give Imadazole 2

Sources & evidence

ORD record
ord-72e5c72bf12d4aacb12142fb1729007d
Source dataset
uspto-grants-2013_09
Patent number
US08541418B2

Reaction notes

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