Triethylamine → HCID 178471183, compound

HRID 1272861Notes

Reaction equation

HRID 1272861 reaction equation
[C:1]([O:5][C:6]([CH3:9])(C)C)(=[O:4])NN.C(N(CC)CC)C.Cl.C(O[NH:21][CH2:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][N:27]=[C:26]2[C:32]1[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=1)C.[NH2:39][NH:40][C:41]([CH2:43][CH2:44]C([O-])=O)=O>C(O)C.ClCCl>[F:38][C:35]1[CH:36]=[CH:37][C:32]([C:26]2[C:25]3[C:29](=[CH:30][CH:31]=[C:23]([C:22]4[NH:21][C:41]([CH2:43][CH2:44][C:1]([O:5][CH2:6][CH3:9])=[O:4])=[N:40][N:39]=4)[CH:24]=3)[NH:28][N:27]=2)=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 70091tert-Butyl carbazateHCID 22479865HCID 22479865, compoundHCID 22480281HCID 22480281, compound

Product 1

HCID 178471183HCID 178471183, compoundYield 16.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a round bottom flask under a nitrogen atmosphere containing tert-butyl carbazate (1.0 g, 0.008 mol) was added dichloromethane (16 mL) and triethylamine (1.06 mL, 0.008 mol). The flask was placed in an ice bath and to the reaction was added ethyl glytaryl chloride (1.38 mL, 0.0088 mol). The reaction was allowed to stir at room temperature overnight. Solvent was removed and the material was taken up in anhydrous ethanol. Gaseous hydrochloric acid was bubbled into the reaction and a solid crashed out of solution that was collected by filtration. This compound was determined to be ethyl 3-(N-aminocarbamoyl)propanoate. To a round bottom flask was added ethoxy[3-(4-fluorophenyl)(1H-indazol-5-yl)]methylamine hydrochloride (200 mg, 0.62 mmol), triethylamine (0.25 mL, 1.86 mmol), and 3-(N-aminocarbamoyl)propanoate (243 mg, 1.25 mmol). This was taken up in anhydrous ethanol (10 mL) and molecular sieves were added to the reaction mixture. The reaction was allowed to stir at 75° C. overnight while under a nitrogen atmosphere. The solvent was removed and the material was purified by preparative HPLC (30–100% acetonitrile over 20 minutes) to yield the title compound (38 mg, 16% yield). Retention time 9.764 minutes 20–100% ODS 1 mL/min; ES-MS m/z 380 [M+H]+.

Workup

  1. customThe flask was placed in an ice bath and to the reaction
  2. additionwas added ethyl glytaryl chloride (1.38 mL, 0.0088 mol)
  3. customSolvent was removed
  4. customGaseous hydrochloric acid was bubbled into the reaction
  5. filtrationwas collected by filtration
  6. additionmolecular sieves were added to the reaction mixture
  7. stirringto stir at 75° C. overnight while under a nitrogen atmosphere
  8. customThe solvent was removed
  9. customthe material was purified by preparative HPLC (30–100% acetonitrile over 20 minutes)

Sources & evidence

ORD record
ord-b5c595e6e1444a4093f488d5a4a1ceae
Source dataset
uspto-grants-2007_04
Patent number
US07208513B2

Reaction notes

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