Triethylamine → HCID 57989054, compound

HRID 471196Notes

Reaction equation

HRID 471196 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[Si]([O:32][CH2:33][CH2:34][C:35]1[C:36]([F:53])=[C:37]([CH:50]=[CH:51][CH:52]=1)[CH2:38][N:39]1[CH2:49][CH2:48][C:42]2([O:47][CH2:46][CH2:45][NH:44][CH2:43]2)[CH2:41][CH2:40]1)(C(C)(C)C)(C)C.[CH:54]([C:57]1[N:62]=[C:61]([C:63](O)=[O:64])[CH:60]=[CH:59][CH:58]=1)([CH3:56])[CH3:55].C(N(CC)CC)C>CN(C=O)C>[F:53][C:36]1[C:35]([CH2:34][CH2:33][OH:32])=[CH:52][CH:51]=[CH:50][C:37]=1[CH2:38][N:39]1[CH2:40][CH2:41][C:42]2([O:47][CH2:46][CH2:45][N:44]([C:63]([C:61]3[CH:60]=[CH:59][CH:58]=[C:57]([CH:54]([CH3:56])[CH3:55])[N:62]=3)=[O:64])[CH2:43]2)[CH2:48][CH2:49]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 219925966-(Propan-2-yl)pyridine-2-carboxylic acidHCID 579891399-(3-(2-(tert-Butyldimethylsilyloxy)ethyl)-2-fluorobenzyl)-1-oxa-4,9-diazaspiro[5.5]undecane

Product 1

HCID 57989054HCID 57989054, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.20 g) was added to a solution of 9-(3-(2-(tert-butyldimethylsilyloxy)ethyl)-2-fluorobenzyl)-1-oxa-4,9-diazaspiro[5.5]undecane (example 78, step d) (0.17 g), 6-isopropylpicolinic acid (example 85, step d) (0.07 g) and triethylamine (0.22 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 (100 mL) and brine (100 mL). The organic phase was separated, washed with brine (2×100 mL), dried over sodium sulphate, filtered and the solvent evaporated. The residue was dissolved in THF (10 mL) and a solution of TBAF in THF (1M, 0.8 mL) was added. The resulting mixture was stirred for 2 h and the solvent evaporated. Purification was 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 (50 mL) was added and the solvent evaporated under reduced pressure to give the subtitled compound as a clear gum. Yield 0.2 g.

Workup

  1. customThe mixture was partitioned between ethyl acetate (100 mL) and brine (100 mL)
  2. customThe organic phase was separated
  3. washwashed with brine (2×100 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customthe solvent evaporated
  7. dissolutionThe residue was dissolved in THF (10 mL)
  8. additiona solution of TBAF in THF (1M, 0.8 mL) was added
  9. stirringThe resulting mixture was stirred for 2 h
  10. customthe solvent evaporated
  11. customPurification
  12. washeluting with 47.5:47.5:5 isohexane
  13. additionThe fractions containing product
  14. additiontoluene (50 mL) was added
  15. customthe solvent evaporated under reduced pressure

Sources & evidence

ORD record
ord-7417c3cc21864545bd72927da5542819
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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