Tetrahydrofuran → 4-{[6-(2,6-dichlorophenyl)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl]amino}-1-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]pyridinium bromide

HRID 1520734Notes

Reaction equation

HRID 1520734 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:25](=[O:26])[N:24]([CH3:27])[C:12]2[N:13]=[C:14]([NH:17][C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)[N:15]=[CH:16][C:11]=2[CH:10]=1.[CH3:28]CN(CCOC1C=CC(NC2N=C3C(C=C(C4C(Cl)=CC=CC=4Cl)C(N3C)=O)=CN=2)=CC=1)CC.C1COCC1.[Br:68]C[C:70]1[N:71]([CH3:78])[CH:72]=[C:73]([N+:75]([O-:77])=[O:76])[N:74]=1>CN1C(=O)CCC1>[Br-:68].[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[C:9]1[C:25](=[O:26])[N:24]([CH3:27])[C:12]2[N:13]=[C:14]([NH:17][C:18]3[CH:23]=[CH:22][N+:21]([CH2:28][C:72]4[N:71]([CH3:78])[CH:70]=[N:74][C:73]=4[N+:75]([O-:77])=[O:76])=[CH:20][CH:19]=3)[N:15]=[CH:16][C:11]=2[CH:10]=1

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 53113826-(2,6-Dichlorophenyl)-2-((4-(2-(diethylamino)ethoxy)phenyl)amino)-8-methylpyrido(2,3-d)pyrimidin-7(8H)-oneHCID 53278892-aminopyrido[2,3-d]pyrimidin-7(8H)-one 42HCID 668237632-(bromomethyl)-1-methyl-4-nitro-1H-imidazole

Product 1

HCID 469380194-{[6-(2,6-dichlorophenyl)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl]amino}-1-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]pyridinium bromideYield 65%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a stirred solution of 6-(2,6-dichlorophenyl)-8-methyl-2-(4-pyridinylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (PD166285 analogue A; Klutchko et al, J Med Chem, 1998, 41(17), 3276-3292) (200 mg, 0.50 mmol) in dry NMP (3 mL)/THF (200 mL) was added 5-(bromomethyl)-1-methyl-4-nitro-1H-imidazole (105) (133 mg, 0.60 mmol). The resulting solution was then stirred at room temperature for 25 days before THF was removed. The resulting solution was partitioned between EtOAc/water. The aqueous portion was subjected to freeze drying and the resulting gum was triturated with Et2O/EtOAc/CH2Cl2 to give 4-{[6-(2,6-dichlorophenyl)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl]amino}-1-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]pyridinium bromide (142) (200 mg, 65%) as a pale yellow powder, m.p. 252° C. (dec). 1H NMR [(CD3)2SO] δ 11.83 (bs, 1H), 9.08 (s, 1H), 8.68 (d, J=7.0 Hz, 2H), 8.21 (bs, 2H), 8.09 (s, 1H), 8.05 (s, 1H), 7.61 (dd, J=8.1, 0.6 Hz, 2H), 7.5 (dd, J=8.9, 7.4 Hz, 1H), 6.00 (s, 2H), 3.84 (s, 3H), 3.73 (s, 3H). Analysis found: C, 44.33; H, 3.42; N, 17.00. C24H19BrCl2N8O3.2H2O requires: C, 44.06; H, 3.54; N, 17.13.

Workup

  1. customwas removed
  2. customThe resulting solution was partitioned between EtOAc/water
  3. customto freeze drying
  4. customthe resulting gum was triturated with Et2O/EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-ee0e0ddfb86746f1a6e08c8e18b2d5bc
Source dataset
uspto-grants-2015_07
Patent number
US09073916B2

Reaction notes

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