Tetrabutylammonium Fluoride → HCID 89690827, compound

HRID 595511Notes

Reaction equation

HRID 595511 reaction equation
S1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[CH:16]=[C:15]([NH:17][CH:18]([CH3:20])[CH3:19])[C:14]([C:21]4[O:22][C:23]([NH:26][CH2:27][CH2:28][CH2:29][O:30][Si](C(C)(C)C)(C)C)=[N:24][N:25]=4)=[CH:13][N:12]=3)[CH:8]=[CH:9][C:4]=2N=C1.CCC[CH2:41][N+:42](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[OH:30][CH2:29][CH2:28][CH2:27][NH:26][C:23]1[O:22][C:21]([C:14]2[C:15]([NH:17][CH:18]([CH3:20])[CH3:19])=[CH:16][C:11]([NH:10][C:7]3[CH:6]=[CH:5][C:4]([C:41]#[N:42])=[CH:9][CH:8]=3)=[N:12][CH:13]=2)=[N:25][N:24]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 89689560HCID 89689560, compound

Product 1

HCID 89690827HCID 89690827, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N2-(benzo[d]thiazol-6-yl)-5-(5-((3-((tert-butyldimethylsilyl)oxy)propyl)amino)-1,3,4-oxadiazol-2-yl)-N4-isopropylpyridine-2,4-diamine (52a) (150 mg, 0.2 mmol) in THF (10 mL) was cooled to 0° C. Added TBAF (1M in THF) (2 equiv.) to the reaction mixture. Reaction mixture was warmed to room temperature and stirred for 1 h. Reaction mixture was quenched by using 10% NaHCO3 solution. The aqueous layer was extracted with EtOAc (twice). The organic layers were collected together, dried over Na2SO4, filtered and concentrated. The crude material was purified by column chromatography through silica gel and MeOH:DCM as eluent. The material obtained was further purified by prep HPLC to provide the desired compound, 4-((5-(5-((3-hydroxypropyl)amino)-1,3,4-oxadiazol-2-yl)-4-(isopropylamino)pyridin-2-yl)amino)benzonitrile. 1H NMR: 400 MHz, CD3OD: δ 1.35 (d, J=6.40 Hz, 6H), 1.89-1.96 (m, 2H), 3.46 (t, J=6.80 Hz, 2H), 3.71 (t, J=6.00 Hz, 2H), 3.79-3.83 (m, 1H), 6.21 (s, 1H), 7.58-7.65 (m, 3H), 7.73-7.76 (m, 2H), 8.37 (s, 1H). LC/MS: XBridge Phe 8, 4.6×30 mm, 3.5 μm; Solvent A=2% ACN: 98% H2O: 10 mM NH4COOH; Solvent B=98% ACN: 2% H2O: 10 mM NH4COOH; gradient 0-100% B over 1.5 min (3.2 min run time); retention time: 1.486 min; LCMS (ES-API), m/z 394.0 (M+H). HPLC: Sunfire C18 (150×4.6 mm), 3.5 micron; Solvent A=5% ACN: 95% H2O: 0.05% TFA pH=2.5; Solvent B=95% ACN: 5% H2O: 0.05% TFA pH=2.5; gradient 0-100% B over 15 min (23 min run time); Flow rate: 1.0 μL/min; Retention time: 5.812 min; Purity: 99.4%.

Workup

  1. customReaction mixture
  2. customReaction mixture
  3. customwas quenched
  4. extractionThe aqueous layer was extracted with EtOAc (twice)
  5. customThe organic layers were collected together
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by column chromatography through silica gel and MeOH
  10. customThe material obtained
  11. customwas further purified by prep HPLC

Sources & evidence

ORD record
ord-baeb72c31381428b9237c82719ef2d33
Source dataset
uspto-grants-2016_01
Patent number
US09242976B2

Reaction notes

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