Acetic Anhydride → HCID 66806562, compound

HRID 1057196Notes

Reaction equation

HRID 1057196 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1/[C:9](/[CH2:31][CH3:32])=[C:10](\[C:20]1[CH:25]=[CH:24][C:23](/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29])=[CH:22][CH:21]=1)/[C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][N:15]=[CH:14]2.[C:33](OC(=O)C)(=[O:35])[CH3:34]>C(Cl)Cl.CN(C)C1C=CN=CC=1>[C:33]([N:16]1[C:17]2[C:13](=[CH:12][C:11](/[C:10](/[C:20]3[CH:25]=[CH:24][C:23](/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29])=[CH:22][CH:21]=3)=[C:9](/[C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[Cl:1])\[CH2:31][CH3:32])=[CH:19][CH:18]=2)[CH:14]=[N:15]1)(=[O:35])[CH3:34]

Participants

5

Reactant 2

HCID 7918Acetic AnhydrideHCID 56941241Brilanestrant2×

Product 1

HCID 66806562HCID 66806562, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (E)-3-(4-((E)-2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylic acid (0.25 g, 0.56 mmol; Compound 195) in DCM (5.6 mL) at room temperature, acetic anhydride (57 mg, 0.56 mmol) was added followed by N,N-dimethylpyridin-4-amine (6 mg, 0.056 mmol). The reaction was stirred at room temperature over the weekend, quenched with water, and then extracted with DCM (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 silica gel column using 0-20% ethyl acetate in hexanes to afford the title compound. 1H NMR (400 MHz, DMSO-d6): δ 12.34 (br, 1H), 8.52 (s, 1H), 8.30 (d, 1H), 7.80 (s, 1H), 7.50 (d, 1H), 7.45-7.40 (m, 5H), 7.20-7.10 (m, 1H), 6.94 (d, 2H), 6.39 (d, 1H), 2.77 (s, 3H), 2.34 (q, 2H), 0.87 (t, 3H); LCMS: 489 (M+H)+.

Workup

  1. customquenched with water
  2. extractionextracted with DCM (2×50 mL)
  3. washThe combined organic layers were washed with water, brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude product
  8. customThis crude material was purified on a silica gel column

Sources & evidence

ORD record
ord-44393533fc30475d8c465eb5840a3987
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

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