Lithium Hydroxide → HCID 178480012, compound

HRID 1628091Notes

Reaction equation

HRID 1628091 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([O:13]C)=[O:12])=[CH:8][CH:9]=2)[C:4]([C:15]2[N:27](S(C3C=CC(C)=CC=3)(=O)=O)[C:18]3=[N:19][CH:20]=[C:21]4[CH:25]=[N:24][N:23]([CH3:26])[C:22]4=[C:17]3[CH:16]=2)=[CH:3]1.[OH-].[Na+].[Li+].[OH-]>O1CCOCC1.O>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([OH:13])=[O:12])=[CH:8][CH:9]=2)[C:4]([C:15]2[NH:27][C:18]3=[N:19][CH:20]=[C:21]4[CH:25]=[N:24][N:23]([CH3:26])[C:22]4=[C:17]3[CH:16]=2)=[CH:3]1

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 14798Sodium HydroxideHCID 58382155HCID 58382155, compound

Product 1

HCID 178480012HCID 178480012, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a flask was added methyl 1-methyl-3-(1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridin-7-yl)-1H-indole-5-carboxylate (0.42 g, 0.82 mmol, prepared using D from Preparation #1 with methyl 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-5-carboxylate [Preparation #19]) and NaOH (0.30 g, 7.5 mmol) in 1,4-dioxane (10 mL) and water (2 mL). The mixture was heated to about 85° C. After about 1 h, LiOH (0.196 g, 8.18 mmol) was added and heating was continued at about 100° C. for about 5 h. The mixture was cooled and concentrated under reduced pressure to remove most of the organics. The mixture was diluted with water (30 mL) then adjusted to about pH 4 with AcOH. The mixture was filtered and the solids washed with water (5 mL). The solids were dried to a constant weight under vacuum at about 60° C. to give 1-methyl-3-(1-methyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridin-7-yl)-1H-indole-5-carboxylic acid the title compound (0.17 g, 60%): LC/MS (Table 2, Method a) Rt=1.73 min; MS m/z 346 (M+H)+. Syk IC50=A.

Workup

  1. temperatureheating
  2. waitwas continued at about 100° C. for about 5 h
  3. temperatureThe mixture was cooled
  4. concentrationconcentrated under reduced pressure
  5. customto remove most of the organics
  6. additionThe mixture was diluted with water (30 mL)
  7. filtrationThe mixture was filtered
  8. washthe solids washed with water (5 mL)
  9. customThe solids were dried to a constant weight under vacuum at about 60° C.

Sources & evidence

ORD record
ord-cedef3ed4d474cd4aaa8660e14fdfb53
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

Loading…