Triethylamine → 1-[(5-Fluoro-1H-indol-3-yl)methyl]-2-thioxo-1,2,3,5-tetrahydro-pyrrolo[3,2-d]pyrimidin-4-one

HRID 536101

Reaction equation

HRID 536101 reaction equation
Cl.C(O[C:5]([C:7]1[NH:8][CH:9]=[CH:10][C:11]=1[NH2:12])=[O:6])C.[F:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[NH:19][CH:18]=[C:17]2[CH:23]=O.[BH3-]C#N.[Na+].CCN(CC)CC.C([N:44]=[C:45]=[S:46])(=O)C1C=CC=CC=1>CO>[F:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[NH:19][CH:18]=[C:17]2[CH2:23][N:12]1[C:11]2[CH:10]=[CH:9][NH:8][C:7]=2[C:5](=[O:6])[NH:44][C:45]1=[S:46]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 68284Benzoyl isothiocyanateHCID 2590895-fluoro-1H-indole-3-carbaldehydeHCID 5003444Sodium cyanoborohydride2×HCID 164270913-Amino-2-ethoxycarbonylpyrrole hydrochloride

Product 1

HCID 117023981-[(5-Fluoro-1H-indol-3-yl)methyl]-2-thioxo-1,2,3,5-tetrahydro-pyrrolo[3,2-d]pyrimidin-4-oneYield 21.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3-Amino-1H-pyrrole-2-carboxylic acid ethyl ester hydrochloride (0.10 g, 0.52 mmol) was dissolved in methanol (4 mL) and 5-fluoro-1H-indole-3-carboxaldehyde (0.10 g, 0.63 mmol), NaCNBH3 (0.033 g, 0.52 mmol) and Et3N (0.073 g, 0.52 mmol) were added. The resulting mixture was stirred at r.t. overnight. Additional NaCNBH3 (0.01 g) was added and the mixture was heated at 50° C. for 5 h. The reaction mixture was cooled to r.t. and concentrated in vacuo. The crude intermediate was dissolved in CH2Cl2 (3 mL) and methanol (1 mL). Benzoyl isothiocyanate (0.078 mL, 0.58 mmol) was added and after stirring at r.t. for 1 h the mixture was concentrated in vacuo. The residue was dissolved in ammonia (7N in methanol, 3 mL) and heated at 80° C. for 2 h. The solvent was removed in vacuo and after purification by preparative HPLC, the title compound (0.035 g, 21%) was obtained as a solid.

Workup

  1. temperaturethe mixture was heated at 50° C. for 5 h
  2. temperatureThe reaction mixture was cooled to r.t.
  3. concentrationconcentrated in vacuo
  4. dissolutionThe crude intermediate was dissolved in CH2Cl2 (3 mL)
  5. stirringafter stirring at r.t. for 1 h the mixture
  6. concentrationwas concentrated in vacuo
  7. dissolutionThe residue was dissolved in ammonia (7N in methanol, 3 mL)
  8. temperatureheated at 80° C. for 2 h
  9. customThe solvent was removed in vacuo
  10. customafter purification by preparative HPLC

Sources & evidence

ORD record
ord-a04e86668dd74bb18d635926ec5be031
Source dataset
uspto-grants-2014_10
Patent number
US08859568B2

Linked notes

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