5-{2-[3-(1-Hydroxy-ethyl)-phenylamino]-pyrimidin-4-yl}-thiophene-2-carboxylic acid methoxy-methyl-amide → 1-(5-{2-[3-(1-Hydroxy-ethyl)-phenylamino]-pyrimidin-4-yl}-thiophen-2-yl)-ethanone

HRID 1012193Notes

Reaction equation

HRID 1012193 reaction equation
CON(C)[C:4]([C:6]1[S:7][C:8]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([CH:24]([OH:26])[CH3:25])[CH:19]=3)[N:12]=2)=[CH:9][CH:10]=1)=[O:5].[CH3:28][Mg]Br>C1COCC1>[OH:26][CH:24]([C:20]1[CH:19]=[C:18]([NH:17][C:13]2[N:12]=[C:11]([C:8]3[S:7][C:6]([C:4](=[O:5])[CH3:28])=[CH:10][CH:9]=3)[CH:16]=[CH:15][N:14]=2)[CH:23]=[CH:22][CH:21]=1)[CH3:25]

Participants

4

Reactant 2

HCID 594684465-{2-[3-(1-Hydroxy-ethyl)-phenylamino]-pyrimidin-4-yl}-thiophene-2-carboxylic acid methoxy-methyl-amideHCID 178418573HCID 178418573, compound

Product 1

HCID 594684321-(5-{2-[3-(1-Hydroxy-ethyl)-phenylamino]-pyrimidin-4-yl}-thiophen-2-yl)-ethanoneYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

5-{2-[3-(1-Hydroxy-ethyl)-phenylamino]-pyrimidin-4-yl}-thiophene-2-carboxylic acid methoxy-methyl-amide (30 mg, 78 μmol) was dissolved in 5 mL of dry THF and cooled to −78° C. Methylmagnesium bromide (3M in ether, 130 μl, 390 μmol) was added dropwise. The mixture was slowly warmed to room temperature and stirred until all the starting material was consumed (LCMS). The reaction mixture was quenched by addition of a saturated ammonium chloride solution and passed through a Varian Chem Elut cartridge. The crude product was concentrated and purified via flash chromatography (hexanes/ethyl acetate+10% methanol gradient) and preparative HPLC (water/acetonitrile gradient) to give 6.6 mg of 1-(5-{2-[3-(1-Hydroxy-ethyl)-phenylamino]-pyrimidin-4-yl}-thiophen-2-yl)-ethanone as a yellow solid (0.19 μmol, 25%). 1H NMR (500 MHz, DMSO-d6) δ 9.71 (s, 1H), 8.56 (d, J=5 Hz, 1H), 8.07 (d, J=4 Hz, 1H), 7.99 (d, J=4 Hz, 1H), 7.83 (s, 1H), 7.61 (m, 1H), 7.43 (d, J=5 Hz, 1H), 7.25 (t, J=8 Hz, 1H), 6.98 (d, J=8 Hz, 1H), 5.13 (bs, 1H), 4.71 (q, J=6.5 Hz, 1H), 2.57 (s, 3H), 1.36 (d, J=6.5 Hz, 3H). MS: m/z 340 (M+H+).

Workup

  1. temperatureThe mixture was slowly warmed to room temperature
  2. customwas consumed (LCMS)
  3. customThe reaction mixture was quenched by addition of a saturated ammonium chloride solution
  4. concentrationThe crude product was concentrated
  5. custompurified via flash chromatography (hexanes/ethyl acetate+10% methanol gradient) and preparative HPLC (water/acetonitrile gradient)

Sources & evidence

ORD record
ord-3e732fddea2c4f8193725e5afaa61491
Source dataset
uspto-grants-2011_07
Patent number
US07977481B2

Reaction notes

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