N-(1-Hydroxy-2-methylpropan-2-yl)thiourea → 5-{2-[(2-hydroxy-1,1-dimethylethyl)amino]-1,3-thiazol-4-yl}-1-methyl-1H-pyrrole-3-carbonitrile

HRID 1436469Notes

Reaction equation

HRID 1436469 reaction equation
Br[CH2:2][C:3]([C:5]1[N:9]([CH3:10])[CH:8]=[C:7]([C:11]#[N:12])[CH:6]=1)=O.C(C1N(C)C=C(C#N)C=1)(=O)C.[OH:24][CH2:25][C:26]([NH:29][C:30]([NH2:32])=[S:31])([CH3:28])[CH3:27]>C(O)C>[OH:24][CH2:25][C:26]([NH:29][C:30]1[S:31][CH:2]=[C:3]([C:5]2[N:9]([CH3:10])[CH:8]=[C:7]([C:11]#[N:12])[CH:6]=2)[N:32]=1)([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 22768414N-(1-Hydroxy-2-methylpropan-2-yl)thioureaHCID 689024905-acetyl-1-methyl-1H-pyrrole-3-carbonitrileHCID 866186255-(2-bromo-acetyl)-1-methyl-1H-pyrrole-3-carbonitrile

Product 1

HCID 866186245-{2-[(2-hydroxy-1,1-dimethylethyl)amino]-1,3-thiazol-4-yl}-1-methyl-1H-pyrrole-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

The above prepared 2:1 mixture of 5-(2-bromo-acetyl)-1-methyl-1H-pyrrole-3-carbonitrile and 5-acetyl-1-methyl-1H-pyrrole-3-carbonitrile in ethanol (50 mL) was treated with N-(2-Hydroxy-1,1-dimethylethyl)thiourea, prepared in step 2 of Example 52, and heated under reflux. The mixture was filtered while still hot, and the precipitate washed with ethanol, and then partitioned between 1 N sodium carbonate and ethyl acetate. The organic layer was washed with water, dried (anhydrous MgSO4) and evaporated to afford 5-{2-[(2-hydroxy-1,1-dimethylethyl)amino]-1,3-thiazol-4-yl}-1-methyl-1H-pyrrole-3-carbonitrile (1.10 g, 3.98 mmol), as a yellow oil. ANLC 100% at 210-370 nm, 7.8 min; 100% at 248 nm, 7.8 min, the Xterra® RP18 column, 3.5μ, 150×4.6 mm column, 1.2 mL/min, 85/15-5/95 (Ammon. Form. Buff. pH=3.5/ACN+MeOH) for 10 min, hold 4 min. HRMS: calcd for C13H16N4OS [M+H]+, 277.11176; found (ESI, [M+H]+), 277.1126.

Workup

  1. customThe above prepared
  2. customprepared in step 2 of Example 52
  3. temperatureheated
  4. temperatureunder reflux
  5. filtrationThe mixture was filtered while still hot, and the precipitate
  6. washwashed with ethanol
  7. custompartitioned between 1 N sodium carbonate and ethyl acetate
  8. washThe organic layer was washed with water
  9. dry with materialdried (anhydrous MgSO4)
  10. customevaporated

Sources & evidence

ORD record
ord-72cb00e807f0484c921df3b730ad53d4
Source dataset
uspto-grants-2009_11
Patent number
US07618990B2

Reaction notes

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