N-(4-fluoro-3-methoxybenzyl)-6-formyl-2-methylpyrimidine-4-carboxamide → N-(4-fluoro-3-methoxybenzyl)-6-(1-hydroxyethyl)-2-methylpyrimidine-4-carboxamide

HRID 572681Notes

Reaction equation

HRID 572681 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:15]=[C:14]([CH:16]=[O:17])[N:13]=[C:12]([CH3:18])[N:11]=2)=[O:9])=[CH:4][C:3]=1[O:21][CH3:22].[CH3:23][Mg]Br>C1COCC1.CCOCC>[F:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:15]=[C:14]([CH:16]([OH:17])[CH3:23])[N:13]=[C:12]([CH3:18])[N:11]=2)=[O:9])=[CH:4][C:3]=1[O:21][CH3:22]

Participants

5

Reactant 2

HCID 86675901N-(4-fluoro-3-methoxybenzyl)-6-formyl-2-methylpyrimidine-4-carboxamideHCID 178418573HCID 178418573, compound

Product 1

HCID 70978723N-(4-fluoro-3-methoxybenzyl)-6-(1-hydroxyethyl)-2-methylpyrimidine-4-carboxamideYield 47.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of N-(4-fluoro-3-methoxybenzyl)-6-formyl-2-methylpyrimidine-4-carboxamide (2 g, 6.59 mmol, Preparation #8) in THF (200 mL) was cooled to about −78° C. and methyl magnesium bromide was added drop wise (8.79 mL, 26.4 mmol, 3M in ether). Upon completion of addition, the reaction mixture stirred for about 4 h at −78° C. The reaction mixture was quenched with aqueous ammoniumchloride (20 mL) and the product extracted with EtOAc (2×100 mL). The organic layer was washed successively with water (1×50 mL), brine (1×50 mL), dried over sodium sulphate and concentrated under reduced pressure to afford N-(4-fluoro-3-methoxybenzyl)-6-(1-hydroxyethyl)-2-methylpyrimidine-4-carboxamide (1 g, 47.6% yield) as a light yellow solid. 1H NMR (400 MHz, DMSO): δ 9.40 (bs, 1H) 7.95 (s, 1H) 7.17-7.11 (m, 2H) 6.89-6.88 (m, 1H) 5.75-5.71 (m, 1H) 4.49-4.47 (m, 2H) 3.81 (s, 3H) 2.68 (s, 3H) MS m/z=320 (m+H)+.

Workup

  1. additionUpon completion of addition
  2. customThe reaction mixture was quenched with aqueous ammoniumchloride (20 mL)
  3. extractionthe product extracted with EtOAc (2×100 mL)
  4. washThe organic layer was washed successively with water (1×50 mL), brine (1×50 mL)
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6111d47ce0fc46e4ae38fce03e6f3488
Source dataset
uspto-grants-2015_05
Patent number
US09029409B2

Reaction notes

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