Ammonia → HCID 66806654, compound

HRID 1057199Notes

Reaction equation

HRID 1057199 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1/[C:9](/[CH2:37][CH3:38])=[C:10](\[C:26]1[CH:31]=[CH:30][C:29](/[CH:32]=C/C(Cl)=O)=[CH:28][CH:27]=1)/[C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16](C1CCCCO1)[N:15]=[CH:14]2.N.C([N:42]([CH2:45][CH3:46])CC)C.Cl.[O:48]1CCOCC1>CCO.O>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1/[C:9](/[CH2:37][CH3:38])=[C:10](\[C:26]1[CH:27]=[CH:28][C:29](/[CH:32]=[CH:46]/[C:45]([NH2:42])=[O:48])=[CH:30][CH:31]=1)/[C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][N:15]=[CH:14]2

Participants

8

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 86695289HCID 86695289, compound

Product 1

HCID 66806654HCID 66806654, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of (E)-3-(4-((E)-2-(2-chloro-4-fluorophenyl)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acryloyl chloride (0.15 g, 0.27 mmol) in dioxane (2.7 mL) at 0° C., ammonia (2.6 mL, 0.5M solution in dioxane) and triethylamine (0.136 g, 1.35 mmol) were added sequentially. The resulting mixture was warmed to room temperature and stirred for 6 h. The mixture was concentrated down to give a residue that was redissolved in EtOH (5.4 mL). HCl (0.5 mL, 2N HCl in diethyl ether) was added, and the reaction was heated at 70° C. for 4 h. Then, the mixture was diluted with water and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water, brine, dried over sodium sulfate, filtered, and concentrated to give the crude product. This crude material was purified on a RP-C18 column using 40-100% acetonitrile in water in the presence of 0.1% TFA to afford the title compound. NMR (400 MHz, DMSO-d6): δ 13.12 (s, 1H), 8.11 (s, 1H), 7.69 (s, 1H), 7.56 (d, 1H), 7.43 (s, 1H), 7.38-7.30 (m, 2H), 7.26-7.11 (m, 5H), 7.03 (s, 1H), 6.98 (d, 2H), 6.44 (d, 1H), 2.36 (q, 2H), 0.89 (t, 3H). LCMS: 446 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated down
  2. customto give a residue that
  3. temperaturethe reaction was heated at 70° C. for 4 h
  4. extractionextracted with ethyl acetate (2×50 mL)
  5. washThe combined organic layers were washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude product
  10. customThis crude material was purified on a RP-C18 column

Sources & evidence

ORD record
ord-de824795a9174c25a3aa4acae0693767
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

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