Triethylamine → tert-Butyl 4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

HRID 1255297Notes

Reaction equation

HRID 1255297 reaction equation
[CH:1]([C:4]1[S:5][CH:6]=[C:7]([C:9]([OH:11])=O)[N:8]=1)([CH3:3])[CH3:2].Cl.[O:13]1[C:18]2([CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH2:17][NH:16][CH2:15][CH2:14]1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH:1]([C:4]1[S:5][CH:6]=[C:7]([C:9]([N:16]2[CH2:17][C:18]3([CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]3)[O:13][CH2:14][CH2:15]2)=[O:11])[N:8]=1)([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 225730652-(Propan-2-yl)-1,3-thiazole-4-carboxylic acidHCID 66964240Tert-butyl 1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride

Product 1

HCID 57989200tert-Butyl 4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 2-isopropylthiazole-4-carboxylic acid (1 g) and tert-butyl 1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride [WuXi PharmaTech] (1.71 g) in DMF (30 mL) was cooled in an ice bath and treated with triethylamine (2.44 mL) followed by HATU (2.89 g). The ice bath was removed and the mixture was stirred at 20° C. for 1 hour. The 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 using 70% ethyl acetate in isohexane as solvent. Fractions containing the product were evaporated to dryness to afford the subtitled compound. Yield 2.0 g.

Workup

  1. customThe ice bath was removed
  2. customThe mixture was partitioned between ethyl acetate and brine
  3. washthe organic layer was washed twice with brine
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure
  7. customThe crude product was purified by flash silica chromatography
  8. additionFractions containing the product
  9. customwere evaporated to dryness

Sources & evidence

ORD record
ord-e536f974dad9430199ca9f3d1d67675a
Source dataset
uspto-grants-2013_06
Patent number
US08455483B2

Reaction notes

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