Thioglycolic Acid → 2-[2-amino-6-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-pyrimidin-4-ylsulfanyl]-acetamide

HRID 217301Notes

Reaction equation

HRID 217301 reaction equation
[Cl:1][C:2]1[C:3]([C:15]2[CH:20]=[C:19]([S:21]([CH3:23])=O)[N:18]=[C:17]([NH2:24])[N:16]=2)=[C:4]2[CH:13]=[CH:12][CH:11]=[C:10]3[C:5]2=[C:6]([CH:14]=1)[CH2:7][O:8][CH2:9]3.SC[C:27]([OH:29])=O.C([N:33](CC)C(C)C)(C)C.[Cl-].[NH4+].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.C(OCC)(=O)C>[NH2:24][C:17]1[N:18]=[C:19]([S:21][CH2:23][C:27]([NH2:33])=[O:29])[CH:20]=[C:15]([C:3]2[C:2]([Cl:1])=[CH:14][C:6]3[CH2:7][O:8][CH2:9][C:10]4[C:5]=3[C:4]=2[CH:13]=[CH:12][CH:11]=4)[N:16]=1

Participants

9

Reactant 6

HCID 1133Thioglycolic AcidHCID 25517Ammonium ChlorideHCID 81531Diisopropylethylamine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 578987824-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-6-methanesulfinyl-pyrimidin-2-ylamine

Product 1

HCID 578988102-[2-amino-6-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-pyrimidin-4-ylsulfanyl]-acetamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Partially purified 4-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-6-methanesulfinyl-pyrimidin-2-ylamine (100 mg) obtained in Step 5 described above was dissolved in N,N-dimethylformamide (1 mL), mercapto acetic acid (0.058 mL) and N,N-diisopropylethylamine (0.192 mL) were added, and this was stirred under nitrogen atmosphere at 80° C. for one hour. After cooling the obtained mixture to room temperature, N,N-dimethylformamide (2 mL), ammonium chloride (134 mg), 1-hydroxybenzotriazole hydrate (422 mg), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride salt (480 mg), and N,N-diisopropylethylamine (0.432 mL) were added, and this was stirred at room temperature for 13 hours. The reaction solution was diluted with ethyl acetate (30 mL), then washed with aqueous ammonium chloride solution (20 mL×2), water (30 mL×2), and saturated aqueous sodium hydrogen carbonate solution (20 mL×2) successively, and then dried over anhydrous sodium sulfate. The residue obtained after filtration and concentration was purified by silica gel thin layer chromatography (developing solvent; dichloromethane:methanol=9:1), and thus, 2-[2-amino-6-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-pyrimidin-4-ylsulfanyl]-acetamide (compound 314) (62 mg) was obtained as a white solid.

Workup

  1. temperatureAfter cooling the obtained mixture to room temperature
  2. stirringthis was stirred at room temperature for 13 hours
  3. washwashed with aqueous ammonium chloride solution (20 mL×2), water (30 mL×2), and saturated aqueous sodium hydrogen carbonate solution (20 mL×2) successively
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe residue obtained
  6. filtrationafter filtration and concentration
  7. customwas purified by silica gel thin layer chromatography (developing solvent; dichloromethane:methanol=9:1)

Sources & evidence

ORD record
ord-ad3a40efed6d43d880b66852585cdc89
Source dataset
uspto-grants-2012_06
Patent number
US08193351B2

Reaction notes

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