Triethylamine → HCID 68978375, compound

HRID 2105296Notes

Reaction equation

HRID 2105296 reaction equation
[C:1]([O:5][CH2:6][CH3:7])(=[O:4])[CH2:2][SH:3].C(N(CC)CC)C.Cl[C:16]1[C:21]([C:22]#[N:23])=[C:20]([NH:24][C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[N:30]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=2)[N:29]=[CH:28]3)[N:19]=[CH:18][N:17]=1>C1COCC1>[CH2:6]([O:5][C:1](=[O:4])[CH2:2][S:3][C:16]1[C:21]([C:22]#[N:23])=[C:20]([NH:24][C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[N:30]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=2)[N:29]=[CH:28]3)[N:19]=[CH:18][N:17]=1)[CH3:7]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 12185Ethyl Thioglycolate2×HCID 866163794-chloro-6-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrimidine-5-carbonitrile

Product 1

HCID 68978375HCID 68978375, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl thioglycolate (also referred to as mercapto-acetic acid ethyl ester) Compound 4f (0.57 g, 4.75 mmol) and triethylamine (0.78 mL, 5.54 mmol) were added to a solution of 4-chloro-6-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrimidine-5-carbonitrile Compound 4e (1.5 g, 3.96 mmol) in THF (20 mL) at RT under nitrogen. The reaction mixture was refluxed for 6 hours, then partitioned between ethyl acetate and water. The organic layer washed with aqueous 10% NH4Cl, water and brine, then dried (Na2SO4), filtered and the solvent evaporated in vacuo to yield a crude solid. The crude solid was purified via flash chromatography (1% methanol/dichloromethane) to yield {5-cyano-6-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrimidin-4-ylsulfanyl}-acetic acid ethyl ester Compound 4g (0.83 g, 45%) as a solid. 1H NMR (400 MHz, DMSO) δ 9.99 (1H, br s), 8.42 (1H, s), 8.13 (1H, d), 7.82 (1H, d), 7.82 (1H, d, J=8.9 Hz), 7.43 (1H, dd, J=1.9 Hz & 8.9 Hz), 7.36-7.34 (1H, m), 7.11-7.02 (3H, m), 5.69 (2H, s), 4.15-4.10 (4H, m), 1.18 (3H, t); MS (ES+) m/z 463.0 (MH+).

Workup

  1. temperatureThe reaction mixture was refluxed for 6 hours
  2. custompartitioned between ethyl acetate and water
  3. washThe organic layer washed with aqueous 10% NH4Cl, water and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent evaporated in vacuo
  7. customto yield a crude solid
  8. customThe crude solid was purified via flash chromatography (1% methanol/dichloromethane)

Sources & evidence

ORD record
ord-0bcdfad7a33046eea0da0db6e4f999fc
Source dataset
uspto-grants-2009_08
Patent number
US07579356B2

Reaction notes

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