Diisopropylethylamine → HCID 44199456, compound

HRID 2061182Notes

Reaction equation

HRID 2061182 reaction equation
[Si]([O:8][C@H:9]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:12])=O)(C(C)(C)C)(C)C.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:49][N:50]1[C:59]2[C:54](=[CH:55][N:56]=[C:57]([CH3:60])[CH:58]=2)[CH:53]=[C:52]([C:61]2[CH:62]=[C:63]([NH:68]/[C:69](/[NH2:72])=[N:70]/O)[CH:64]=[CH:65][C:66]=2[CH3:67])[C:51]1=[O:73]>CN(C=O)C>[OH:8][C@@H:9]([C:10]1[O:12][N:70]=[C:69]([NH:68][C:63]2[CH:64]=[CH:65][C:66]([CH3:67])=[C:61]([C:52]3[C:51](=[O:73])[N:50]([CH3:49])[C:59]4[C:54]([CH:53]=3)=[CH:55][N:56]=[C:57]([CH3:60])[CH:58]=4)[CH:62]=2)[N:72]=1)[CH:13]([CH3:14])[CH3:15]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14358766HCID 14358766, compoundHCID 178422078HCID 178422078, compound2×

Product 1

HCID 44199456HCID 44199456, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of (R)-2-(tert-butyldimethylsilyloxy)-3-methylbutanoic acid (83 mg, 0.35 mmol) in DMF (2 mL) were added DIPEA (52 μL, 0.3 mmol) and HATU (0.11 g, 0.3 mmol). After stirring at rt for 15 min, 17 (0.10 g, 0.3 mmol) was added as a solution in DMF (1 mL). The reaction was stirred at rt until complete consumption of 17 was determined by LC/MS and then was heated at 100° C. for 1 h. Subsequently, the reaction was cooled to rt, partitioned with EtOAc (30 mL) and 5% aq NaHCO3 (20 mL). The aqueous layer was extracted with fresh EtOAc (2×20 mL). The combined organic layers were dried over magnesium sulfate, filtered and reduced to dryness. The crude material was dissolved in THF and was added TBAF (2.7 mL of a 1.0 M solution in THF). The mixture was stirred at rt for 2 h. Subsequently the reaction was diluted with EtOAc (20 mL) and washed with water and brine. The organic layer was dried over magnesium sulfate, filtered and reduced to dryness. The crude product was purified by preparative LCMS to give (R)-3-(5-(5-(1-hydroxy-2-methylpropyl)-1,2,4-oxadiazol-3-ylamino)-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one (A92). 1H NMR (400 MHz, d6-DMSO) δ 9.87 (s, 1H), 8.81 (s, 1H), 7.94 (s, 1H), 7.43 (s, 1H), 7.39 (dd, J=8, 2 Hz, 1H), 7.30 (d, J=2 Hz, 1H), 7.21 (d, J=8 Hz, 1H), 6.02 (d, J=6 Hz, 1H), 4.48 (bt, J=6 Hz, 1H), 3.67 (s, 3H), 2.61 (s, 3H), 2.07 (s, 3H) 0.94 (d, J=6 Hz, 3H), 0.87 (d, J=6 Hz, 3H). MS m/z 420.4 (M+1).

Workup

  1. temperaturewas heated at 100° C. for 1 h
  2. temperatureSubsequently, the reaction was cooled to rt
  3. custompartitioned with EtOAc (30 mL) and 5% aq NaHCO3 (20 mL)
  4. extractionThe aqueous layer was extracted with fresh EtOAc (2×20 mL)
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. dissolutionThe crude material was dissolved in THF
  8. additionwas added TBAF (2.7 mL of a 1.0 M solution in THF)
  9. stirringThe mixture was stirred at rt for 2 h
  10. additionSubsequently the reaction was diluted with EtOAc (20 mL)
  11. washwashed with water and brine
  12. dry with materialThe organic layer was dried over magnesium sulfate
  13. filtrationfiltered
  14. customThe crude product was purified by preparative LCMS

Sources & evidence

ORD record
ord-003ee803d9e3441e9775b516281c170a
Source dataset
uspto-grants-2012_10
Patent number
US08278452B2

Reaction notes

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