Methanol → HCID 89690832, compound

HRID 595520Notes

Reaction equation

HRID 595520 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:21][C:20]([C:22](OC)=[O:23])=[N:19][N:18]=4)=[C:13]([NH:26][CH:27]([CH3:29])[CH3:28])[CH:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.CO.[Li+].[BH4-]>C1COCC1.CCOC(C)=O>[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:21][C:20]([CH2:22][OH:23])=[N:19][N:18]=4)=[C:13]([NH:26][CH:27]([CH3:29])[CH3:28])[CH:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

6

Reactant 3

HCID 887MethanolHCID 4148881Lithium borohydrideHCID 89690872HCID 89690872, compound

Product 1

HCID 89690832HCID 89690832, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl 5-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazole-2-carboxylate (200 mg) in THF (10 mL):MeOH (10 mL) was cooled to 0° C. Added LiBH4 (3 equiv.) in portions to the reaction mixture, stirred for 30 min at 0° C. Gradually the reaction temperature was raised to room temperature and stirred for 30 min. The reaction was quenched using ice pieces. The reaction mass was concentrated under reduced pressure. The residue obtained was diluted with EtOAc. The organic layer was washed with water. The organic layer was collected, dried over Na2SO4, filtered and concentrated. The crude material obtained was purified by prep HPLC to afford the desired compound, (5-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)methanol. 1H NMR: 400 MHz, DMSO-d6: δ 657.15 (d, J=524681.20 Hz, 6H), 3.71-3.79 (m, 1H), 4.71 (d, J=6.40 Hz, 2H), 5.93 (t, J=6.40 Hz, 1H), 6.21 (s, 1H), 7.36-7.38 (m, 1H), 7.52 (d, J=7.20 Hz, 1H), 7.61 (dd, J=2.00, 8.80 Hz, 1H), 7.97 (d, J=8.80 Hz, 1H), 8.49 (s, 1H), 8.65 (d, J=2.00 Hz, 1H), 9.17 (s, 1H), 9.44 (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: 1.454 min; LCMS (ES-API), m/z 383.2 (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: 5.528 min; Purity: 85.66%.

Workup

  1. customThe reaction was quenched
  2. concentrationThe reaction mass was concentrated under reduced pressure
  3. customThe residue obtained
  4. washThe organic layer was washed with water
  5. customThe organic layer was collected
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material obtained
  10. customwas purified by prep HPLC

Sources & evidence

ORD record
ord-0b468e7e7eb44511ba06d291138c65c0
Source dataset
uspto-grants-2016_01
Patent number
US09242976B2

Reaction notes

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