5-Iodo-4-methoxypyrimidine → 4-Methoxy-5-(2-methoxy-4-nitrophenyl)pyrimidine

HRID 1405081Notes

Reaction equation

HRID 1405081 reaction equation
CC1C=CN=CC=1C1C=CC=C2C=1C=NN2.I[C:18]1[C:19]([O:24][CH3:25])=[N:20][CH:21]=[N:22][CH:23]=1.[CH3:26][O:27][C:28]1[CH:33]=[C:32]([N+:34]([O-:36])=[O:35])[CH:31]=[CH:30][C:29]=1B1OC(C)(C)C(C)(C)O1.CC1(C)C(C)(C)OB(C2C=CC([N+]([O-])=O)=CC=2C)O1>CN(C=O)C>[CH3:25][O:24][C:19]1[C:18]([C:29]2[CH:30]=[CH:31][C:32]([N+:34]([O-:36])=[O:35])=[CH:33][C:28]=2[O:27][CH3:26])=[CH:23][N:22]=[CH:21][N:20]=1

Participants

6

Reactant 4

HCID 105617605-Iodo-4-methoxypyrimidineHCID 248204924,4,5,5-Tetramethyl-2-(2-methyl-4-nitrophenyl)-1,3,2-dioxaborolaneHCID 667086722-(2-Methoxy-4-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 667156544-(4-methylpyridin-3-yl)-1H-indazole

Product 1

HCID 667144434-Methoxy-5-(2-methoxy-4-nitrophenyl)pyrimidineYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Intermediate 30B was prepared by the procedure described for the preparation of Intermediate 1C using Intermediate 30A and 2-(2-methoxy-4-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (prepared by the procedure described for the preparation of Intermediate 26A), and was obtained as a gummy yellow solid. The solid was dissolved in DMF and purified by reverse phase preparative HPLC (PHENOMENEX® Luna 30×100 mm column with a linear gradient of Solvent A (10% methanol/90% water with 0.1% TFA) and Solvent B (90% methanol/10% water with 0.1% TFA) over 12 min; monitored at 254 nM). The collected fractions were then applied to a 1 g Waters OASIS® MCX cation exchange cartridge, which was washed with methanol, and the product was then eluted off with 15 mL of 2 M ammonia in methanol. Evaporation of the collected eluent provided Intermediate 30B (46 mg, 25% yield) as a solid. HPLC Ret timed: 1.34 min. MS: m/z=262 [M+H]+; 1H NMR (500 MHz, CD3OD) δ ppm 8.48 (s, 1 H), 8.05 (s, 1 H), 7.94-7.90 (m, 2 H), 7.57 (d, 1 H), 3.93 (s, 3 H), 3.61 (s, 3 H).

Workup

  1. customIntermediate 30B was prepared by the procedure
  2. customprepared by the procedure
  3. customwas obtained as a gummy yellow solid
  4. custompurified by reverse phase preparative HPLC (PHENOMENEX® Luna 30×100 mm column with a linear gradient of Solvent A (10% methanol/90% water with 0.1% TFA) and Solvent B (90% methanol/10% water with 0.1% TFA) over 12 min
  5. washwas washed with methanol
  6. washthe product was then eluted off with 15 mL of 2 M ammonia in methanol
  7. customEvaporation of the collected eluent

Sources & evidence

ORD record
ord-7def3bfa47124ddeaef047ef22c1d068
Source dataset
uspto-grants-2014_12
Patent number
US08916553B2

Reaction notes

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