Hydrochloric Acid → N-[9-(6-Fluoro-pyridin-2-ylmethyl)-6-trifluoromethoxy-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-isobutyramide

HRID 545546Notes

Reaction equation

HRID 545546 reaction equation
[F:1][C:2]1[N:7]=[C:6]([CH2:8][N:9]2[C:21]3[CH2:20][CH2:19][CH:18]([NH2:22])[CH2:17][C:16]=3[C:15]3[C:10]2=[CH:11][CH:12]=[C:13]([O:23][C:24]([F:27])([F:26])[F:25])[CH:14]=3)[CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:35](Cl)(=[O:39])[CH:36]([CH3:38])[CH3:37].Cl>C(Cl)Cl>[F:1][C:2]1[N:7]=[C:6]([CH2:8][N:9]2[C:21]3[CH2:20][CH2:19][CH:18]([NH:22][C:35](=[O:39])[CH:36]([CH3:38])[CH3:37])[CH2:17][C:16]=3[C:15]3[C:10]2=[CH:11][CH:12]=[C:13]([O:23][C:24]([F:27])([F:25])[F:26])[CH:14]=3)[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 62325Isobutyryl chlorideHCID 574316659-(6-Fluoropyridin-2-ylmethyl)-6-trifluoromethoxy-2,3,4,9-tetrahydro-1H-carbazol-3-ylamine

Product 1

HCID 59161204N-[9-(6-Fluoro-pyridin-2-ylmethyl)-6-trifluoromethoxy-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-isobutyramideYield 52.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dissolve 9-(6-fluoro-pyridin-2-ylmethyl)-6-trifluoromethoxy-2,3,4,9-tetrahydro-1H-carbazol-3-ylamine (Preparation 47) (580 mg, 1.53 mmol) and triethylamine (201 mg, 277 μL, 1.99 mmol) in CH2Cl2 (20 ML). Slowly add isobutyryl chloride (212 mg, 208 μL, 1.99 mmol) and stir at room temperature for 18 h. Dilute the reaction with dilute HCl (10 mL), then load the reaction onto a Varian ChemElut CE1020 solid-phase extraction cartridge (Varian part number 12198008). Elute, collect, and concentrate 125 mL CH2Cl2 to give the crude product (794 mg) as a brown oil. Purify the crude product on silica gel (40 g), eluting with 35-65% EtOAc/hexanes to afford 358 mg (52%) of the title compound as a yellow foam. MS (ES): m/z 450 (M+1), 448 (M−1); HPLC (Method B): Rt=8.21 min (100%).

Workup

  1. additionDilute
  2. customthe reaction
  3. extractiononto a Varian ChemElut CE1020 solid-phase extraction cartridge (Varian part number 12198008)
  4. washElute
  5. customcollect
  6. concentrationconcentrate 125 mL CH2Cl2
  7. customto give the crude product (794 mg) as a brown oil
  8. customPurify the crude product on silica gel (40 g)
  9. washeluting with 35-65% EtOAc/hexanes

Sources & evidence

ORD record
ord-c92654e8b5a243c49f3e6bcb9ec1a432
Source dataset
uspto-grants-2011_05
Patent number
US07935722B2

Reaction notes

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