tert-Butanol → HCID 25001850, compound

HRID 2239504Notes

Reaction equation

HRID 2239504 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([O:27][CH3:28])=[C:17]([N:20]3[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]3)[CH:18]=2)[N:13]=[N:12][C:11]=1[C:29]#[N:30].[OH-].[K+].C([OH:37])(C)(C)C>O>[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([O:27][CH3:28])=[C:17]([N:20]3[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]3)[CH:18]=2)[N:13]=[N:12][C:11]=1[C:29]([NH2:30])=[O:37]

Participants

5

Reactant 3

HCID 6386tert-ButanolHCID 14797Potassium HydroxideHCID 67083771HCID 67083771, compound

Product 1

HCID 25001850HCID 25001850, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 100 mL round bottom flask was charged with 4-(2-fluoro-4-methylphenylamino)-7-methoxy-6-(4-methylpiperazin-1-yl)cinnoline-3-carbonitrile (Method 60) (360 mg, 0.89 mmol) and potassium hydroxide (4.9 g, 88.6 mmol). Anhydrous tert-butyl alcohol (30 ml) was added and the reaction was heated at vigorous reflux 1 h before being allowed to cool to rt. The reaction mixture was then poured into a separatory funnel containing water (˜100 mL) and extracted with EtOAc (2×200 mL). The combined organic layer was washed with sat'd aqueous NaCl (˜100 mL), dried with MgSO4, filtered, and conc. in vacuo to give the crude product which was purified via silica gel chromatography (40 g) using EtOAc/MeOH (1:1) as eluent to give the title compound as a yellow solid. The solid was then recrystallized from 5 mL of MeOH which provided pure title compound (184 mg, 48.9%) as a pale yellow solid. 1HNMR: 11.60 (s, 1H), 8.55 (s, 1H), 7.85 (s, 1H), 7.16 (s, 1H), 7.37 (m, 2H), 7.10 (m, 1H), 6.21 (s, 1H), 4.05 (s, 3H), 2.46 (s, br, 4H), 2.70-2.60 (m, 7H), 2.35 (s, 3H); m/z 425.

Workup

  1. temperaturethe reaction was heated
  2. temperatureat vigorous reflux 1 h
  3. additionThe reaction mixture was then poured into a separatory funnel
  4. extractionextracted with EtOAc (2×200 mL)
  5. washThe combined organic layer was washed with sat'd aqueous NaCl (˜100 mL)
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. customconc. in vacuo to give the crude product which
  9. customwas purified via silica gel chromatography (40 g)

Sources & evidence

ORD record
ord-0472cb02a85a44eeb144e64ab479cdca
Source dataset
uspto-grants-2010_05
Patent number
US07723337B2

Reaction notes

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