Dimethylamine → N-[6-Dimethylamino-9-(3-fluoro-benzyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-isobutyramide

HRID 545502Notes

Reaction equation

HRID 545502 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=1)[C:10]1[CH2:9][CH2:8][CH:7]([NH:23][C:24](=[O:28])[CH:25]([CH3:27])[CH3:26])[CH2:6][C:5]2=1.[CH3:29][NH:30][CH3:31].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)C=CC=CC=1.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[Fe+2]>[CH3:29][N:30]([CH3:31])[C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=1)[C:10]1[CH2:9][CH2:8][CH:7]([NH:23][C:24](=[O:28])[CH:25]([CH3:27])[CH3:26])[CH2:6][C:5]2=1

Participants

8

Reactant 3

HCID 674DimethylamineHCID 23676156Sodium t-butoxideHCID 57431656N-[9-(3-Fluorobenzyl)-6-bromo-2,3,4,9-tetrahydro-1H-carbazol-3-yl]isobutyramide

Product 1

HCID 59161264N-[6-Dimethylamino-9-(3-fluoro-benzyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-isobutyramideYield 74%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a sealed tube, heat N-[6-bromo-9-(3-fluoro-benzyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-isobutyramide (Example 35) (200 mg, 0.45 mmol), dimethyl amine (2.0 M in tetrahydrofuran, 0.45 mL, 0.90 mmol), palladium acetate (5 mg, 0.002 mmol), sodium tert-butoxide (133 mg, 1.38 mmol), and 1,2,3,4,5-pentaphenyl-1′-(di-t-butylphosphino)ferrocene ligand (60 mg, 0.008 mmol) in toluene (5 mL) at 70° C. overnight. Cool to room temperature, dilute with ethyl acetate/10% potassium carbonate, and filter off the red suspension. Wash the organic portion with 10% aqueous potassium carbonate (2×), dry over anhydrous sodium sulfate, filter, and concentrate. Purify the residue by silica gel column chromatography eluting with 40 to 100% ethyl acetate/hexanes to obtain the title compound (135 mg, 74%). MS (ES): m/z 408 (M+1); 1H NMR (CD3OD): δ 7.25 (m, 1H), 7.18 (d, 1H), 7.01 (s, 1H), 6.96 (t, 1H), 6.89 (d, 1H), 6.81 (d, 1H), 6.65 (d, 1H), 5.30 (s, 2H), 4.19 (m, 1H), 3.08 (dd, 1H), 2.88 (s, 6H), 2.77 (m, 2H), 2.63 (m, 1H), 2.50 (m, 1H), 2.12 (m, 1H), 1.97 (m, 1H), 1.18 (m, 6H).

Workup

  1. filtrationfilter off the red suspension
  2. washWash the organic portion with 10% aqueous potassium carbonate (2×)
  3. dry with materialdry over anhydrous sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify the residue by silica gel column chromatography
  7. washeluting with 40 to 100% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-4f9e9aa966974c8186100acdf9b2b1b6
Source dataset
uspto-grants-2011_05
Patent number
US07935722B2

Reaction notes

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