Cesium carbonate → 7-(4-Methoxy-2-methylphenyl)-2,6-dimethyl-N-[(1S)-1-methylpropyl]pyrrolo[1,2-b]pyridazin-4-amine

HRID 1796966Notes

Reaction equation

HRID 1796966 reaction equation
Br[C:2]1[C:3]2[N:4]([C:9]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][C:14]=3[CH3:21])=[C:10]([CH3:12])[CH:11]=2)[N:5]=[C:6]([CH3:8])[CH:7]=1.[C@@H:22]([NH2:26])([CH2:24][CH3:25])[CH3:23].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([C:9]2[N:4]3[N:5]=[C:6]([CH3:8])[CH:7]=[C:2]([NH:26][C@@H:22]([CH3:23])[CH2:24][CH3:25])[C:3]3=[CH:11][C:10]=2[CH3:12])=[C:14]([CH3:21])[CH:15]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2×HCID 67137532-Butanamine, (S)-2×HCID 221747864-Bromo-7-(4-methoxy-2-methylphenyl)-2,6-dimethylpyrrolo[1,2-b]pyridazine

Product 1

HCID 586199647-(4-Methoxy-2-methylphenyl)-2,6-dimethyl-N-[(1S)-1-methylpropyl]pyrrolo[1,2-b]pyridazin-4-amine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 4-bromo-7-(4-methoxy-2-methylphenyl)-2,6-dimethylpyrrolo[1,2-b]pyridazine (0.137 g, 0.397 mmol), (S)-(+)-sec-butylamine (0.08 mL, 0.794 mmol), xantphos (0.025 g, 0.04 mmol), Cs2CO3 (0.18 g, 0.55 mmol) and Pd2(dba)3 (0.018 g, 0.02 mmol) in dioxane (4.0 mL) was refluxed for 17 h. Extra (S)-(+)-sec-butylamine (0.08 mL, 0.794 mmol), xantphos (0.025 g, 0.04 mmol) and Pd2(dba)3 (0.018 g, 0.02 mmol) were added to the reaction mixture and refluxed for additional 4 h. After cooling to room temperature, the mixture was filtered through a pad of celite. The filtrate was concentrated in vacuo to dryness, the residue was subjected to column chromatography (silica gel, 1/10 EtOAc/heptane) to give 0.024 g (18%) of light yellow oil as the title compound. 1H NMR (300 MHz, CDCl3) δ 7.23 (d, J=11 Hz, 1H), 6.89 (d, J=4 Hz, 1H), 6.83 (dd, J=4, 11 Hz, 1H), 6.29 (br s, 1H), 5.54 (s, 1H), 3.87 (s, 3H), 3.64–3.56 (m, 1H), 2.32 (s, 3H), 2.16 (s, 3H), 2.11 (s, 3H), 1.77–1.57 (m, 2H), 1.32–1.28 (m, 3H), 1.06–0.99 (m, 3H); MS m/z 338.4 (M++H).

Workup

  1. temperaturewas refluxed for 17 h
  2. temperaturerefluxed for additional 4 h
  3. filtrationthe mixture was filtered through a pad of celite
  4. concentrationThe filtrate was concentrated in vacuo to dryness

Sources & evidence

ORD record
ord-08435f8646144509ad724c50bf3ced46
Source dataset
uspto-grants-2006_04
Patent number
US07034023B2

Reaction notes

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