Diisobutylaluminum hydride → [6-(Thiazolo[4,5-b]pyridin-2-yloxy)-1H-indol-2-yl]-methanol

HRID 1947462Notes

Reaction equation

HRID 1947462 reaction equation
C[O:2][C:3]([C:5]1[NH:6][C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[C:9]([O:14][C:15]1[S:16][C:17]3[C:18]([N:23]=1)=[N:19][CH:20]=[CH:21][CH:22]=3)[CH:8]=2)=O.CC(C[AlH]CC(C)C)C.[NH4+].[Cl-]>C(Cl)Cl>[S:16]1[C:17]2[C:18](=[N:19][CH:20]=[CH:21][CH:22]=2)[N:23]=[C:15]1[O:14][C:9]1[CH:8]=[C:7]2[C:12]([CH:13]=[C:5]([CH2:3][OH:2])[NH:6]2)=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 14487Diisobutylaluminum hydrideHCID 25517Ammonium ChlorideHCID 687723426-(Thiazolo[4,5-b]pyridin-2-yloxy)-1H-indole-2-carboxylic acid methyl ester

Product 1

HCID 66786455[6-(Thiazolo[4,5-b]pyridin-2-yloxy)-1H-indol-2-yl]-methanolYield 31.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) solution of 6-(thiazolo[4,5-b]pyridin-2-yloxy)-1H-indole-2-carboxylic acid methyl ester (1.0 g, 3.1 mmol) in DCM (30 mL) was added DIBALH (1 M in THF, 15.4 mL, 13.2 g, 15.4 mmol) and the reaction mixture was stirred (0° C., 2 h). The reaction mixture was treated with saturated aqueous NH4Cl (1 mL), partitioned with EtOAc (50 mL) and saturated aqueous Rochelle's salt (50 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (2×50 mL). The organic layer was dried, filtered and concentrated in vacuo. The resulting residue was purified by silica gel flash chromatography using MeOH (0.2 M NH3):DCM (0-15%) to provide the title compound as yellow solid (287 mg, 31%). MS (ESI): mass calcd. for C16H11N3O2S, 297.1; m/z found, 298.0 [M+H]+. 1H NMR (400 MHz, CDCl3/CD3OD 10:1): 8.49 (dd, J=4.9, 1.6, 1H), 7.99 (dd, J=7.9, 1.6, 1H), 7.53 (d, J=8.5, 1H), 7.43 (d, J=2.0, 1H), 7.20 (dd, J=7.9, 4.9, 1H), 6.99 (dd, J=8.5, 2.2, 1H), 6.36 (s, 1H), 4.77 (s, 2H).

Workup

  1. custompartitioned with EtOAc (50 mL) and saturated aqueous Rochelle's salt (50 mL)
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×50 mL)
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-56d87de1fcef4e008188044a19a2e338
Source dataset
uspto-grants-2013_03
Patent number
US08399465B2

Reaction notes

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