Tetrahydrofuran → HCID 53261780, compound

HRID 60111Notes

Reaction equation

HRID 60111 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]([C:13]3[C:14]([F:27])=[C:15]([NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22])[CH:16]=[CH:17][C:18]=3[F:19])=[O:12])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.C(N(CC)CC)C.[CH3:35][C:36]1[O:40][NH:39][CH:38]([C:41](Cl)=[O:42])[CH:37]=1.O1CCCC1>O.N1C=CC=CC=1>[F:27][C:14]1[C:15]([NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:22])=[O:23])=[CH:16][CH:17]=[C:18]([F:19])[C:13]=1[C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([NH:1][C:41]([CH:38]3[CH:37]=[C:36]([CH3:35])[O:40][NH:39]3)=[O:42])[CH:3]=2)[NH:8][CH:9]=1)=[O:12]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 583687962,3-Dihydro-5-methyl-3-isoxazolecarbonyl chlorideHCID 58368819HCID 58368819, compound

Product 1

HCID 53261780HCID 53261780, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

In a reaction vial, propane-1-sulfonic acid [3-(5-amino-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide (39, crude material e.g. from Scheme 5, step 2) is mixed with triethylamine (0.0363 mL, 0.26 mmol), 5-methyl-2,3-dihydro-isoxazole-3-carbonyl chloride (40, 45.4 mg, 0.312 mmol), 1 mL of tetrahydrofuran, and 1 mL of pyridine. The reaction is stirred at room temperature for 16 hours, then diluted with water, and extracted 3× with ethyl acetate. The combined organic layers are washed 2× with brine, dried with sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is further purified by reverse phase chromatography and the resulting material confirmed by LC-MS.

Workup

  1. extractionextracted 3× with ethyl acetate
  2. washThe combined organic layers are washed 2× with brine
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under vacuum
  6. customThe resulting material is further purified by reverse phase chromatography

Sources & evidence

ORD record
ord-a953489faff044829528fa1b7157488c
Source dataset
uspto-grants-2016_09
Patent number
US09440969B2

Reaction notes

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