Trifluoroacetic acid → HCID 25177157, compound

HRID 1811736Notes

Reaction equation

HRID 1811736 reaction equation
C([O:5][C:6](=O)[C:7]1[CH:12]=[C:11]([C:13]2[CH:18]=[C:17]([S:19][CH2:20][CH2:21][C:22](=[O:30])[NH:23][CH2:24][CH2:25][O:26][CH2:27][CH2:28][NH2:29])[N:16]=[C:15]([NH2:31])[N:14]=2)[C:10]([CH3:32])=[CH:9][C:8]=1[CH3:33])(C)(C)C.FC(F)(F)C(O)=O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.Cl.C(N=C=NCCCN(C)C)C>ClCCl>[NH2:31][C:15]1[N:16]=[C:17]2[CH:18]=[C:13]([C:11]3[CH:12]=[C:7]([C:6](=[O:5])[NH:29][CH2:28][CH2:27][O:26][CH2:25][CH2:24][NH:23][C:22](=[O:30])[CH2:21][CH2:20][S:19]2)[C:8]([CH3:33])=[CH:9][C:10]=3[CH3:32])[N:14]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 757711-Hydroxybenzotriazole2×HCID 81531Diisopropylethylamine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 59224681HCID 59224681, compound

Product 1

HCID 25177157HCID 25177157, compoundYield 3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-(2-Amino-6-{2-[2-(2-aminoethoxy)ethylcarbamoyl]ethylsulfanyl}pyrimidin-4-yl)-2,4-dimethylbenzoic acid tert-butyl ester (78 mg, 0.159 mmol) obtained in Step 1 above was dissolved in dichloromethane (3 ml), and then trifluoroacetic acid (1 ml) was added thereto. After this solution was stirred at room temperature for two hours, the solvent was distilled off under reduced pressure. The resulting crude product was dissolved in a mixed solvent of N,N-dimethylformamide (25 ml) and tetrahydrofuran (75 ml), and then 1-hydroxybenzotriazole (134 mg, 0.795 mmol), diisopropylethylamine (137 μl, 0.795 mmol), and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (152 mg, 2.2 mmol) were sequentially added thereto. After the solution was stirred at room temperature for 16 hours, 1-hydroxybenzotriazole (270 mg, 1.59 mmol), diisopropylethylamine (274 μl, 1.59 mmol), and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (304 mg, 1.59 mmol) were added thereto. After the solution was stirred at 50° C. for seven hours, the solvent was distilled off under reduced pressure. The residue was diluted with ethyl acetate. The ethyl acetate solution was washed with a saturated aqueous sodium bicarbonate solution (twice), and dried over anhydrous sodium sulfate. After the inorganic salt was removed by filtration, the filtrate was concentrated. The resulting residue was purified by preparative thin layer silica gel chromatography (developing solvent: dichloromethane:methanol=15:1). The obtained crude product was washed with dichloromethane to yield 4-amino-20,22-dimethyl-14-oxa-7-thia-3,5,11,17-tetraazatricyclo[17.3.1.12,6]tetracosa-1(22),2(24),3,5,19(23),20-hexaene-10,18-dione (Compound 29) (2 mg) as a white solid material.

Workup

  1. distillationthe solvent was distilled off under reduced pressure
  2. dissolutionThe resulting crude product was dissolved in a mixed solvent of N,N-dimethylformamide (25 ml) and tetrahydrofuran (75 ml)
  3. stirringAfter the solution was stirred at room temperature for 16 hours
  4. stirringAfter the solution was stirred at 50° C. for seven hours
  5. distillationthe solvent was distilled off under reduced pressure
  6. additionThe residue was diluted with ethyl acetate
  7. washThe ethyl acetate solution was washed with a saturated aqueous sodium bicarbonate solution (twice), and
  8. dry with materialdried over anhydrous sodium sulfate
  9. customAfter the inorganic salt was removed by filtration
  10. concentrationthe filtrate was concentrated
  11. customThe resulting residue was purified by preparative thin layer silica gel chromatography (developing solvent: dichloromethane:methanol=15:1)
  12. customThe obtained crude product
  13. washwas washed with dichloromethane

Sources & evidence

ORD record
ord-c537bd31bff047b1b22a04020603c40a
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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