4-(Tributylstannyl)pyridazine → HCID 66611837, compound

HRID 1812167Notes

Reaction equation

HRID 1812167 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:17]2[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([N:24]([CH2:34][C:35]3[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=3)[CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[N:18]=2)[C:5]([NH:8][C:9]2[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)=[N:6][CH:7]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C([Sn](CCCC)(CCCC)[C:82]1[CH:87]=[CH:86][N:85]=[N:84][CH:83]=1)CCC>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]>[CH3:33][O:32][C:29]1[CH:30]=[CH:31][C:26]([CH2:25][N:24]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[C:19]2[N:18]=[C:17]([C:4]3[C:5]([NH:8][C:9]4[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=4)=[N:6][CH:7]=[C:2]([C:82]4[CH:87]=[CH:86][N:85]=[N:84][CH:83]=4)[CH:3]=3)[N:22]=[C:21]([CH3:23])[N:20]=2)=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 64097334-(Tributylstannyl)pyridazineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 666119674-(5-chloro-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 66611837HCID 66611837, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
110 °C

Procedure

4-(5-chloro-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (190 mg, 0.325 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (15.51 mg, 0.033 mmol) (Strem Chemicals), tris(dibenzylideneacetone)dipalladium(0) (14.89 mg, 0.016 mmol) (Strem Chemicals) and 4-(tributylstannyl)pyridazine (156 mg, 0.423 mmol) (Synthonix) were weighed in a vial, purged with argon, and then treated with toluene (1.6 mL). The vial was sealed and heated at 110° C. in an oil bath for 21 h. The reaction mixture was treated with water and extracted with EtOAc (2×30 mL), washed with brine (20 mL) and dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography using an ISCO Combiflash Companion (12 g column, 20-100% EtOAc in hexanes) to give N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-(pyridazin-4-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (157.1 mg, 0.250 mmol, 77% yield) as a bright yellow crystalline solid. m/z (ESI, +ve ion) 628.0 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 11.96 (1H, s); 9.44 (1H, d, J=1.4 Hz); 9.16 (1H, d, J=5.1 Hz); 9.10 (1H, d, J=2.7 Hz); 8.64 (1H, d, J=2.7 Hz); 8.30 (1H, d, J=2.5 Hz); 7.88 (1H, dd, J=8.7, 2.6 Hz); 7.58 (1H, dd, J=5.4, 2.6 Hz); 7.23 (2H, d, J=8.6 Hz); 7.17 (2H, d, J=8.8 Hz); 6.87 (4H, dd, J=12.7, 8.6 Hz); 6.75 (1H, d, J=8.8 Hz); 4.91 (2H, s); 4.83 (2H, s); 3.95 (3H, s); 3.81 (3H, s); 3.78 (3H, s); 2.62 (3H, s).

Workup

  1. custompurged with argon
  2. additiontreated with toluene (1.6 mL)
  3. customThe vial was sealed
  4. additionThe reaction mixture was treated with water
  5. extractionextracted with EtOAc (2×30 mL)
  6. washwashed with brine (20 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-d2bbeed926d24068afc40b2a6003209d
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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