Aluminium lithium hydride → HCID 89689787, compound

HRID 877553Notes

Reaction equation

HRID 877553 reaction equation
[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[N:16]=[CH:15][C:14]([C:17]4[O:18][C:19]([CH:27]([CH3:29])[CH3:28])=[C:20]([C:22](OCC)=[O:23])[N:21]=4)=[C:13]([NH:30][CH:31]([CH3:33])[CH3:32])[CH:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>O1CCCC1>[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[N:16]=[CH:15][C:14]([C:17]4[O:18][C:19]([CH:27]([CH3:29])[CH3:28])=[C:20]([CH2:22][OH:23])[N:21]=4)=[C:13]([NH:30][CH:31]([CH3:33])[CH3:32])[CH:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 89689847HCID 89689847, compound

Product 1

HCID 89689787HCID 89689787, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylate (29) (150 mg, 0.34 mmol) in dry Tetrahydrofuran (10 mL) was added LAH (0.739 mmol) (4% in THF) at −10° C. The reaction mixture was stirred at 0° C. for 30 min, reaction temperature was then brought to room temperature and stirred for 30 min. The reaction mixture was cooled to 0° C. and quenched by using ice flakes (until the H2 gas evolution ceased), followed by 1N NaOH solution, filtered through celite, precipitate was washed with ethyl acetate. The organic layers were combined, dried over Na2SO4, filtered and concentrated in vacuum to give crude compound. The crude material was purified by flash column chromatography using silica gel and ethyl acetate/hexane as eluent to provide (2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-5-isopropyloxazol-4-yl)methanol. 1H NMR: 400 MHz, DMSO-d6: δ 1.28-1.30 (m, 12H), 3.68-3.73 (m, 1H), 4.38-4.39 (m, 2H), 5.03-5.03 (m, 1H), 6.15 (s, 1H), 7.57 (dd, J=2.00, 8.80 Hz, 1H), 7.95 (d, J=8.80 Hz, 1H), 8.11 (d, J=6.80 Hz, 1H), 8.54 (s, 1H), 8.74 (d, J=1.60 Hz, 1H), 9.15 (s, 1H), 9.30 (s, 1H). LC/MS: ZORBAX SB C18, 4.6×50 mm, 5 μm; Solvent A=10% MeOH: 90% H2O: 0.1% TFA; Solvent B=90% MeOH: 10% H2O: 0.1% TFA; gradient 0-100% B over 2 min (3 min run time); retention time: 1.703 min; LCMS (ES-API), m/z 424.0 (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: 6.663 min; Purity: 99.2%.

Workup

  1. customreaction temperature
  2. customwas then brought to room temperature
  3. stirringstirred for 30 min
  4. temperatureThe reaction mixture was cooled to 0° C.
  5. customquenched
  6. filtrationfiltered through celite, precipitate
  7. washwas washed with ethyl acetate
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuum
  11. customto give crude compound
  12. customThe crude material was purified by flash column chromatography

Sources & evidence

ORD record
ord-c4648b08c18d486c9740d88d39446735
Source dataset
uspto-grants-2015_03
Patent number
US08987311B2

Reaction notes

Loading…