1,2-Dichloroethane → HCID 66802025, compound

HRID 1057197Notes

Reaction equation

HRID 1057197 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]=[CH:33]/[C:34]([OH:36])=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.[CH3:39][S:40]([NH2:43])(=[O:42])=[O:41].C(Cl)CCl.Cl>CN(C1C=CN=CC=1)C.C1COCC1.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:31]=[CH:30][C:29](/[CH:32]=[CH:33]/[C:34]([NH:43][S:40]([CH3:39])(=[O:42])=[O:41])=[O:36])=[CH:28][CH:27]=1)/[C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][N:15]=[CH:14]2

Participants

9

Reactant 4

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 72879MethanesulfonamideHCID 66793378HCID 66793378, compound2×

Product 1

HCID 66802025HCID 66802025, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture 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)acrylic acid (0.26 g, 0.5 mmol; Compound 407), DMAP (92 mg, 0.75 mmol), methane sulfonamide (0.19 g, 2 mmol) and EDC (0.14 g, 0.75 mmol) in THF (2.5 mL) was stirred at room temperature overnight. The reaction mixture was quenched with 1N HCl, diluted with water, and extracted with ethyl acetate (2×50 mL). The combined organic layers were concentrated to give the crude product that was purified on a silica gel column using 5% methanol in DCM to afford a pale yellow solid. This solid was redissolved in EtOH (5 mL), and then HCl (1 mL, 1.25 N HCl in ethanol) was added. The reaction was heated at 70° C. for 3 h, cooled to room temperature, diluted with water, and then 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. 1H NMR (300 MHz, DMSO-d6): δ 13.13 (s, 1H), 11.80 (s, 1H), 8.11 (s, 1H), 7.70 (s, 1H), 7.63-7.53 (m, 2H), 7.39-7.30 (m, 4H), 7.21-7.12 (m, 2H), 7.00 (d, 2H), 6.49 (d, 1H), 3.28 (s, 3H), 2.36 (q, 2H), 0.89 (t, 3H). LCMS: 524 (M+H)+.

Workup

  1. customThe reaction mixture was quenched with 1N HCl
  2. additiondiluted with water
  3. extractionextracted with ethyl acetate (2×50 mL)
  4. concentrationThe combined organic layers were concentrated
  5. customto give the crude product that
  6. customwas purified on a silica gel column
  7. customto afford a pale yellow solid
  8. temperatureThe reaction was heated at 70° C. for 3 h
  9. temperaturecooled to room temperature
  10. extractionextracted with ethyl acetate (2×50 mL)
  11. washThe combined organic layers were washed with water, brine
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customto give the crude product
  16. customThis crude material was purified on a RP-C18 column

Sources & evidence

ORD record
ord-91c8b2aae28f43d9ba1a8c136b3c2786
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

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