Triethylamine → (9-(2-Fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isobutylthiazol-4-yl)methanone

HRID 471156

Reaction equation

HRID 471156 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[O:25]1[C:30]2([CH2:35][CH2:34][N:33]([CH2:36][C:37]3[C:38]([F:46])=[C:39]([CH2:43][CH2:44][OH:45])[CH:40]=[CH:41][CH:42]=3)[CH2:32][CH2:31]2)[CH2:29][NH:28][CH2:27][CH2:26]1.[CH2:47]([C:51]1[S:52][CH:53]=[C:54]([C:56](O)=[O:57])[N:55]=1)[CH:48]([CH3:50])[CH3:49].C(N(CC)CC)C>CN(C=O)C>[F:46][C:38]1[C:39]([CH2:43][CH2:44][OH:45])=[CH:40][CH:41]=[CH:42][C:37]=1[CH2:36][N:33]1[CH2:34][CH2:35][C:30]2([O:25][CH2:26][CH2:27][N:28]([C:56]([C:54]3[N:55]=[C:51]([CH2:47][CH:48]([CH3:50])[CH3:49])[S:52][CH:53]=3)=[O:57])[CH2:29]2)[CH2:31][CH2:32]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 235881542-(2-Methylpropyl)-1,3-thiazole-4-carboxylic acidHCID 579891872-(3-(1-Oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-2-fluorophenyl)ethanol

Product 1

HCID 57989373(9-(2-Fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isobutylthiazol-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.2 g) was added to a solution of 2-(3-(1-oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-2-fluorophenyl)ethanol (example 67, step f) (0.13 g), 2-isobutylthiazole-4-carboxylic acid (example 72, step d) (0.08 g) and triethylamine (0.23 mL) in DMF (7 mL) at 0° C. and the resulting yellow solution allowed to warm to RT and was stirred for 2 h. The mixture was partitioned between ethyl acetate and brine (100 mL), the organic phase was washed with brine (2×100 mL), dried over sodium sulphate, filtered and then evaporated. The resulting gum was purified by silica gel chromatography eluting with 47.5:47.5:5 isohexane:ethyl acetate:triethylamine to 95:5 ethyl acetate:triethylamine gradient. The fractions containing product were combined, toluene (200 mL) was added, and the solvent evaporated under reduced pressure to give the subtitled compound as a clear gum. Yield 0.24 g.

Workup

  1. customThe mixture was partitioned between ethyl acetate and brine (100 mL)
  2. washthe organic phase was washed with brine (2×100 mL)
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. customevaporated
  6. customThe resulting gum was purified by silica gel chromatography
  7. washeluting with 47.5:47.5:5 isohexane
  8. additionThe fractions containing product
  9. additiontoluene (200 mL) was added
  10. customthe solvent evaporated under reduced pressure

Sources & evidence

ORD record
ord-348eddfeecba4416aa2ba64c02fca9ef
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Linked notes

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