p-Toluenesulfonic acid monohydrate → HCID 123398049, compound

HRID 1056957Notes

Reaction equation

HRID 1056957 reaction equation
[NH2:1][C:2]1[C:3]([O:28][C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:30]=2[F:36])=[C:4]([C:9]2[C:10]3[CH:19]=[CH:18][N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:11]=3[C:12](=[O:16])[N:13]([CH3:15])[CH:14]=2)[CH:5]=[CH:6][C:7]=1[NH2:8].[CH:37]([O-])([O-])OCC.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCCC1.C(OCC)(=O)C.O>[F:36][C:30]1[CH:31]=[C:32]([F:35])[CH:33]=[CH:34][C:29]=1[O:28][C:3]1[C:2]2[N:1]=[CH:37][NH:8][C:7]=2[CH:6]=[CH:5][C:4]=1[C:9]1[C:10]2[CH:19]=[CH:18][N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:26])([CH3:27])[CH3:25])[C:11]=2[C:12](=[O:16])[N:13]([CH3:15])[CH:14]=1

Participants

7

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 53630039EthylorthoformateHCID 123986855HCID 123986855, compound

Product 1

HCID 123398049HCID 123398049, compoundYield 81%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 4-[3,4-diamino-2-(2,4-difluorophenoxyl)phenyl]-6-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (460 mg, 0.897 mmol) in tetrahydrofuran (7.76 mL) was treated with ethyl orthoformate (448 μL, 2.69 mmol) followed by addition of p-toluenesulfonic acid monohydrate (17.1 mg, 0.0897 mmol). The resultant reaction mixture was stirred at 50° C. for 1 h, after which time the reaction mixture was diluted with ethyl acetate and water. Layers were separated and the organic layer was washed with brine, dried with magnesium sulfate, filtered, and concentrated in vacuo to give the crude product. Purification by gradient flash column chromatography (50% EtOAc/hexanes to 100% EtOAc) gave the desired product (0.378 g, 81%). LCMS calculated for C27H29F2N4O3Si (M+H)+: m/z=523.2. found: 523.2.

Workup

  1. customThe resultant reaction mixture
  2. customLayers were separated
  3. washthe organic layer was washed with brine
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give the crude product
  8. customPurification by gradient flash column chromatography (50% EtOAc/hexanes to 100% EtOAc)

Sources & evidence

ORD record
ord-1a5aff81930546388451ae8d55ce180c
Source dataset
uspto-grants-2016_07
Patent number
US09399640B2

Reaction notes

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