p-Toluenesulfonic acid monohydrate → HCID 178442277, compound

HRID 2174137Notes

Reaction equation

HRID 2174137 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[N:9])=[CH:4][C:3]=1[NH:10][C:11](=O)[C:12]([C:17]1[C:25](OC)=[CH:24][C:23]([CH3:28])=[C:22]2[C:18]=1[CH:19]=[CH:20][N:21]2C(OC(C)(C)C)=O)([CH3:16])[CH2:13][CH:14]=[CH2:15].[OH2:37].[C:38]1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.O1CCOCC1>[CH3:38][O:37][C:25]1[C:17]([C:12]([C:11]2[NH:1][C:2]3[CH:7]=[CH:6][C:5]([C:8]#[N:9])=[CH:4][C:3]=3[N:10]=2)([CH2:13][CH:14]=[CH2:15])[CH3:16])=[C:18]2[C:22](=[C:23]([CH3:28])[CH:24]=1)[NH:21][CH:20]=[CH:19]2

Participants

5

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrate3×HCID 86701783HCID 86701783, compound

Product 1

HCID 178442277HCID 178442277, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
135 °C

Procedure

(±)-tert-Butyl 4-(1-((2-amino-5-cyanophenyl)amino)-2-methyl-1-oxopent-4-en-2-yl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 156-E) (0.36 g, 0.737 mmol) was dissolved in toluene (2.76 mL) and dioxane (0.921 mL). p-Toluenesulfonic acid monohydrate (0.042 g, 0.221 mmol) was then added and the mixture heated at 135° C. for 3 hours. At this point another aliquot of p-toluenesulfonic acid monohydrate (0.030 g) was added and the reaction was heated for 1 hour. At this point another aliquot of p-toluenesulfonic acid monohydrate (0.025 g) was added and the reaction was heated for 1.5 hour. The reaction was then cooled to room temperature, concentrated and absorbed onto silica to purify via FCC(0-50% EtOAc:heptanes) to obtain the title compound that was used directly in the next step. MS (ESI+) m/z 371.4 (M+H).

Workup

  1. temperaturethe reaction was heated for 1 hour
  2. temperaturethe reaction was heated for 1.5 hour
  3. temperatureThe reaction was then cooled to room temperature
  4. concentrationconcentrated
  5. customabsorbed onto silica
  6. customto purify via FCC(0-50% EtOAc:heptanes)

Sources & evidence

ORD record
ord-dc586aa69f2245048911c67b27d93f16
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

Loading…