4-Iodo-2-methoxynicotinaldehyde → HCID 178494185, compound

HRID 2377770Notes

Reaction equation

HRID 2377770 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:19]=[C:18]([CH3:20])[C:17]([NH2:21])=[C:16]([N+:22]([O-])=O)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H].[I:27][C:28]1[CH:33]=[CH:32][N:31]=[C:30]([O:34][CH3:35])[C:29]=1[CH:36]=O.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1>CO.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:15]=[C:16]3[C:17]([N:21]=[C:36]([C:29]4[C:30]([O:34][CH3:35])=[N:31][CH:32]=[CH:33][C:28]=4[I:27])[NH:22]3)=[C:18]([CH3:20])[N:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 100383814-Iodo-2-methoxynicotinaldehydeHCID 12217721Iodo benzene diacetateHCID 69277210HCID 69277210, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 178494185HCID 178494185, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent3×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 4-(5-amino-4-methyl-6-nitro-pyrimidin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (3.18 g, 9.4 mmol) in methanol (200 mL) and 10% palladium on carbon (180 mg) were added methanol (10 mL) under nitrogen. The reaction mixture was stirred under hydrogen atmosphere (hydrogen balloon) for 18 hours. The solution was filtered through a pad of celite and the filtercake was washed with a small amount of MeOH. This solution was cooled to 0° C. and the 4-iodo-2-methoxy-pyridine-3-carbaldehyde (2.47 g, 9.4 mmol) in methanol (50 mL) was added to the reaction mixture and stirred at 23° C. for 18 hours. Then iodobenzene diacetate (3.03 g, 9.4 mmol) was added and the reaction mixture was stirred at 23° C. for 5 hours. MeOH was evaporated in vacuo and the crude material was purified on silica gel column using EtOAc:Hex (1:2 to 1:1 gradient) to give the title compound as a yellow solid. (2.75 g, 53%). HPLC 98%. LCMS (+ESI, M+H+) m/z 552; IR (KBr, cm−1) 3177, 2976, 1699, 1558, 1223; 1H NMR (400 MHz, DMSO) δ 12.92 (s, 1H), 8.0 (d, J=5.1 Hz, 1H), 7.64 (d, J=5.6 Hz, 1H), 3.81 (s, 3H), 3.73 (br s, 4H), 3.43 (br s, 4H), 2.57 (s, 3H), 1.44 (s, 9H).

Workup

  1. filtrationThe solution was filtered through a pad of celite
  2. washthe filtercake was washed with a small amount of MeOH
  3. stirringthe reaction mixture was stirred at 23° C. for 5 hours
  4. customMeOH was evaporated in vacuo
  5. customthe crude material was purified on silica gel column

Sources & evidence

ORD record
ord-27a303e4ebbc49b2b10e6c3e3f3af00e
Source dataset
uspto-grants-2008_12
Patent number
US07470696B2

Reaction notes

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