HCID 71060942, compound → HCID 71060876, compound

HRID 1911033Notes

Reaction equation

HRID 1911033 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]3[CH2:20][CH2:19][CH2:18][C:17]([C:21](OC)=[O:22])=[C:16]([CH3:25])[C:15]=3[CH:26]=2)=[O:9])=[N:6][CH:7]=1.CC(C[AlH]CC(C)C)C.C1COCC1>C1COCC1.[Cl-].[Na+].O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]3[CH2:20][CH2:19][CH2:18][C:17]([CH2:21][OH:22])=[C:16]([CH3:25])[C:15]=3[CH:26]=2)=[O:9])=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 71060942HCID 71060942, compoundHCID 131729343Dibal-H thf

Product 1

HCID 71060876HCID 71060876, compoundYield 37.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of methyl 2-(5-chloropicolinamido)-9-methyl-6,7-dihydro-5H-benzo[7]annulene-8-carboxylate from step 3A (345 mg, 0.930 mmol) in THF (2 mL) was slowly added 1.0 M DIBAL-H/THF (4.65 mL, 4.65 mmol) at −78° C. The mixture was stirred at −78° C. for 4 h and then allowed to warm to rt. Brine was added slowly to quench the reaction. The reaction mixture was then extracted with 3×100 mL of EtOAc and the organic layers were combined, dried over sodium sulfate, and concentrated. The residue was purified using silica gel column chromatography (hexanes-60% EtOAc) to give a clean (E)-5-chloro-N-(8-(hydroxymethyl)-9-methyl-6,7-dihydro-5H-benzo[7]annulen-2-yl)picolinamide (120 mg, 0.350 mmol, 37.6% yield). LCMS (M+H)+=343.2. 1H NMR (500 MHz, chloroform-d) δ 9.81 (s, 1H), 8.56 (dd, J=2.3, 0.6 Hz, 1H), 8.25 (dd, J=8.4, 0.6 Hz, 1H), 7.87 (dd, J=8.4, 2.3 Hz, 1H), 7.66 (d, J=2.3 Hz, 1H), 7.55 (dd, J=8.1, 2.3 Hz, 1H), 7.18 (d, J=8.2 Hz, 1H), 4.39 (s, 2H), 2.54 (t, J=7.0 Hz, 2H), 2.14 (s, 3H), 2.10 (quin, J=7.1 Hz, 2H), 2.01-1.95 (m, 2H)

Workup

  1. customat −78° C
  2. temperatureto warm to rt
  3. customto quench
  4. customthe reaction
  5. extractionThe reaction mixture was then extracted with 3×100 mL of EtOAc
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified

Sources & evidence

ORD record
ord-346d488cbd3f422db65df3d8f8e66953
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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