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

HRID 471153Notes

Reaction equation

HRID 471153 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.[CH3:47][CH2:48][CH:49]([C:52]1[S:53][CH:54]=[C:55]([C:57](O)=[O:58])[N:56]=1)[CH2:50][CH3:51].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:57]([C:55]3[N:56]=[C:52]([CH:49]([CH2:50][CH3:51])[CH2:48][CH3:47])[S:53][CH:54]=3)=[O:58])[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 579605932-(Pentan-3-yl)thiazole-4-carboxylic acidHCID 579891872-(3-(1-Oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-2-fluorophenyl)ethanol

Product 1

HCID 57989379(9-(2-Fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-(pentan-3-yl)thiazol-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-(pentan-3-yl)thiazole-4-carboxylic acid (example 71, step d) (0.081 g) and triethylamine (0.23 mL) in DMF (7 mL) at 0° C. The resulting yellow solution was 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 a as clear gum. Yield 0.25 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-283f766f7558486d9906c1e72e377bef
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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