Triethylamine → 1,1-Dimethylethyl 10-[(2-methyl-4-thiazolyl)carbonyl]-7-oxa-3,10-diazaspiro[5.6]dodecane-3-carboxylate

HRID 471211Notes

Reaction equation

HRID 471211 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:25]1[C:30]2([CH2:36][CH2:35][NH:34][CH2:33][CH2:32][O:31]2)[CH2:29][CH2:28][N:27]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:26]1.[CH3:44][C:45]1[S:46][CH:47]=[C:48]([C:50](O)=[O:51])[N:49]=1.C(N(CC)CC)C>CN(C=O)C>[CH3:44][C:45]1[S:46][CH:47]=[C:48]([C:50]([N:34]2[CH2:35][CH2:36][C:30]3([CH2:29][CH2:28][N:27]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:26][CH2:25]3)[O:31][CH2:32][CH2:33]2)=[O:51])[N:49]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2847282-Methyl-1,3-thiazole-4-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57989265Tert-butyl 7-oxa-3,10-diazaspiro[5.6]dodecane-3-carboxylate

Product 1

HCID 579893211,1-Dimethylethyl 10-[(2-methyl-4-thiazolyl)carbonyl]-7-oxa-3,10-diazaspiro[5.6]dodecane-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

HATU (0.322 g) was added in one portion to a solution at 0° C. of tert-butyl 7-oxa-3,10-diazaspiro[5.6]dodecane-3-carboxylate (example 89, step e) (0.176 g) and 2-methylthiazole-4-carboxylic acid (0.093 g) and triethylamine (0.36 mL) in DMF (10 mL). The mixture was then stirred at 20° C. for 1 hour. The reaction mixture was partitioned between ethyl acetate and brine. The organic layer was washed twice with brine, dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography eluting with ethyl acetate. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 210 mg.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and brine
  2. washThe organic layer was washed twice with brine
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. customthe solvent evaporated under reduced pressure
  6. customThe crude product was purified by flash silica chromatography
  7. washeluting with ethyl acetate
  8. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-07bc0f3917c047d791aa43f8924cf75e
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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