Triethylamine → (2-(3-(2-Hydroxyethyl)phenethyl)-5-oxa-2,8-diazaspiro[3.5]nonan-8-yl)(2-isopropylthiazol-4-yl)methanone

HRID 446482Notes

Reaction equation

HRID 446482 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[CH2:27]1[C:30]2([CH2:35][NH:34][CH2:33][CH2:32][O:31]2)[CH2:29][N:28]1[CH2:36][CH2:37][C:38]1[CH:39]=[C:40]([CH2:44][CH2:45][OH:46])[CH:41]=[CH:42][CH:43]=1.[CH:47]([C:50]1[S:51][CH:52]=[C:53]([C:55](O)=[O:56])[N:54]=1)([CH3:49])[CH3:48].C(N(CC)CC)C>CN(C=O)C>[OH:46][CH2:45][CH2:44][C:40]1[CH:39]=[C:38]([CH:43]=[CH:42][CH:41]=1)[CH2:37][CH2:36][N:28]1[CH2:29][C:30]2([CH2:35][N:34]([C:55]([C:53]3[N:54]=[C:50]([CH:47]([CH3:49])[CH3:48])[S:51][CH:52]=3)=[O:56])[CH2:33][CH2:32][O:31]2)[CH2:27]1

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 66964399HCID 66964399, compound

Product 1

HCID 58168481(2-(3-(2-Hydroxyethyl)phenethyl)-5-oxa-2,8-diazaspiro[3.5]nonan-8-yl)(2-isopropylthiazol-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

HATU (0.792 g) was added in one portion to a stirred solution at 0° C. of 2-(3-(2-(5-oxa-2,8-diazaspiro[3.5]nonan-2-yl)ethyl)phenyl)ethanol 2HCl (0.56 g) (example 176 step e), 2-isopropylthiazole-4-carboxylic acid (0.275 g) and triethylamine (1.117 ml) in DMF (7 mL). The mixture was stirred at 20° C. for 3 hours and then partitioned between ethyl acetate and brine, the organic layer was washed with brine (×2), dried, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography, 5% methanol in ethyl acetate with 1% triethylamine. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.475 g

Workup

  1. custompartitioned between ethyl acetate and brine
  2. washthe organic layer was washed with brine (×2)
  3. customdried
  4. filtrationfiltered
  5. customthe solvent evaporated under reduced pressure
  6. customThe crude product was purified by flash silica chromatography, 5% methanol in ethyl acetate with 1% triethylamine
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-b2cea27c5847416caa6107c62196bd6e
Source dataset
uspto-grants-2013_07
Patent number
US08476265B2

Reaction notes

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