Diethyl Ether → HCID 46938025, compound

HRID 1520735Notes

Reaction equation

HRID 1520735 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:34](=[O:35])[N:33]([CH3:36])[C:12]2[N:13]=[C:14]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)=[CH:20][CH:19]=3)[N:15]=[CH:16][C:11]=2[CH:10]=1.[Br:37][CH2:38][C:39]1[N:43]([CH3:44])[CH:42]=[N:41][C:40]=1[N+:45]([O-:47])=[O:46].CCOCC>CN1C(=O)CCC1>[Br-:37].[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[C:9]1[C:34](=[O:35])[N:33]([CH3:36])[C:12]2[N:13]=[C:14]([NH:17][C:18]3[CH:19]=[CH:20][C:21]([O:24][CH2:25][CH2:26][N+:27]4([CH2:38][C:39]5[N:43]([CH3:44])[CH:42]=[N:41][C:40]=5[N+:45]([O-:47])=[O:46])[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]4)=[CH:22][CH:23]=3)[N:15]=[CH:16][C:11]=2[CH:10]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 5327913HCID 5327913, compoundHCID 24950639HCID 24950639, compound

Product 1

HCID 46938025HCID 46938025, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a stirred solution of 6-(2,6-dichlorophenyl)-8-methyl-2-{4-[2-(1-piperidinyl)ethoxy]anilino}pyrido[2,3-d]pyrimidin-7(8H)-one (PD 166285 analogue B; Klutchko et al, J Med Chem, 1998, 41(17), 3276-3292) (230 mg, 0.44 mmol) in dry NMP (5 mL) was added 5-(bromomethyl)-1-methyl-4-nitro-1H-imidazole (122) (116 mg, 0.53 mmol). The resulting solution was then stirred at room temperature for 12 days before Et2O was added. The resulting precipitate was filtered and washed with EtOAc and CH2Cl2. The crude product was purified by precipitation from NMP/EtOAc (×2). The precipitate was filtered and dried under vacuum to give 1-[2-(4-{[6-(2,6-dichlorophenyl)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl]amino}phenoxy)ethyl]-1-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]piperidinium bromide (143) (100 mg, 31%) as a pale yellow powder, m.p. 176-178° C. 1H NMR [(CD3)2SO] δ 10.14 (s, 1H), 8.82 (s, 1H), 8.14 (s, 1H), 7.89 (s, 1H), 7.80 (d, J=8.9 Hz, 2H), 7.59 (dd, J=8.1, 0.7 Hz, 2H), 7.46 (dd, J=8.8, 7.4 Hz, 1H), 7.10 (d, J=9.1 Hz, 2H), 5.22 (bs, 2H), 4.61 (t, J=4.4 Hz, 2H), 4.17 (bs, 2H), 3.86 (s, 3H), 3.72-3.64 (m, 2H), 3.65 (s, 3H), 2.10-1.95 (m, 4H), 1.74 (bd, J=14.3 Hz, 2H), 1.60 (bd, J=14.3 Hz, 1H), 1.46-1.31 (m, 1H), 2 protons not observed. Analysis found: C, 48.33; H, 4.64; N, 13.32. C32H33BrCl2N8O4.3H2O.¼EtOAc requires: C, 48.31; H, 5.04; N, 13.66.

Workup

  1. additionwas added
  2. filtrationThe resulting precipitate was filtered
  3. washwashed with EtOAc and CH2Cl2
  4. customThe crude product was purified by precipitation from NMP/EtOAc (×2)
  5. filtrationThe precipitate was filtered
  6. customdried under vacuum

Sources & evidence

ORD record
ord-239d554044474df2be55e08f0ee72366
Source dataset
uspto-grants-2015_07
Patent number
US09073916B2

Reaction notes

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