Cesium carbonate → 7-(2,4-dichlorophenyl)-N-(1-ethylpropyl)-2,6-dimethylpyrrolo[1,2-b]pyridazin-4-amine

HRID 1791154Notes

Reaction equation

HRID 1791154 reaction equation
Br[C:2]1[C:3]2[N:4]([C:9]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])=[C:10]([CH3:12])[CH:11]=2)[N:5]=[C:6]([CH3:8])[CH:7]=1.C1(PC2C=CC=CC=2)C=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:40]([CH:42]([NH2:45])[CH2:43][CH3:44])[CH3:41]>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]>[Cl:20][C:14]1[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=1[C:9]1[N:4]2[N:5]=[C:6]([CH3:8])[CH:7]=[C:2]([NH:45][CH:42]([CH2:43][CH3:44])[CH2:40][CH3:41])[C:3]2=[CH:11][C:10]=1[CH3:12]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 120193-Pentanamine2×HCID 70017Diphenylphosphine2×HCID 220281714-Bromo-7-(2,4-dichlorophenyl)-2,6-dimethylpyrrolo[1,2-b]pyridazine

Product 1

HCID 99295567-(2,4-dichlorophenyl)-N-(1-ethylpropyl)-2,6-dimethylpyrrolo[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-(2,4-dichlorophenyl)-2,6-dimethylpyrrolo[1,2-b]pyridazine (0.253 g, 0.683 mmol), 5-(diphenylphosphino)-9,9-dimethyl-9H-xanthen-4-yl](diphenyl)phosphine (0.043 g, 0.068 mmol), Cs2CO3 (0.311 g, 0.956 mmol) and Pd2(dba)3 (0.031 g, 0.034 mmol) in dioxane (7.0 mL) is stirred at room temperature for 5 min followed by the addition of 1-ethylpropylamine (0.16 mL, 0.119 g, 1.37 mmol). The resulting mixture is refluxed for 10 h. After cooling to room temperature, 5-(diphenylphosphino)-9,9-dimethyl-9H-xanthen-4-yl](diphenyl)phosphine (0.022 g, 0.034 mmol), Pd2(dba)3 (0.016 g, 0.017 mmol) and 1-ethylpropylamine (0.08 mL, 0.06 g, 0.68 mmol) are added and the mixture is refluxed for an additional 7 h. The mixture is filtered through a pad of celite and washed with EtOAc. The filtrate is concentrated in vacuo to dryness, the residue is subjected to preparative TLC (silica gel, 1/15 EtOAc/heptane) to give 0.167 g (65%) of light yellow oil as the title compound. The product is solidified and recrystalized from pet ether to give a light yellow solid: mp 115–118° C.; 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J=2.1 Hz, 1H), 7.43 (d, J=8.3 Hz, 1H), 7.36 (dd, J=2.1, 8.3 Hz, 1H), 6.32 (s, 1H), 5.58 (s, 1H), 4.21 (d, J=8.7 Hz, 1H), 3.50–3.42 (m, 1H), 2.33 (s, 3H), 2.23 (s, 3H), 1.79–1.69 (m, 2H), 1.63–1.56 (m, 2H), 1.04–0.98 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 153.9, 143.5, 136.7, 134.7, 134.5, 130.2, 130.0, 127.1, 123.1, 120.8, 119.9, 94.9, 88.3, 55.3, 27.5, 22.8, 12.7, 10.7; IR (liq.) 2965, 2929, 2326, 1996, 1748, 1614, 1563, 1487, 1461, 1443, 1374, 1333, 1002, 821, 813 cm−1; MS (EI) m/z 378 (M++H), 376 (M++H); HRMS (FAB) calcd for C20H23Cl2N3+H 376.1347, found 376.1353; Anal. Calcd for C20H23Cl2N3: C, 63.83; H, 6.16; N, 11.17. Found: C, 63.93; H, 6.23; N, 11.12.

Workup

  1. temperatureThe resulting mixture is refluxed for 10 h
  2. temperatureAfter cooling to room temperature
  3. temperaturethe mixture is refluxed for an additional 7 h
  4. filtrationThe mixture is filtered through a pad of celite
  5. washwashed with EtOAc
  6. concentrationThe filtrate is concentrated in vacuo to dryness

Sources & evidence

ORD record
ord-75dba5912e8f4575b66e9d0fa05114ac
Source dataset
uspto-grants-2006_07
Patent number
US07074791B2

Reaction notes

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