Hydrazine hydrate (1:1) → (S)-[4-(2-Amino-pyridin-3-ylmethyl)-7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester

HRID 2427270Notes

Reaction equation

HRID 2427270 reaction equation
[CH:1]([O:4][C:5](=[O:39])[NH:6][C@@H:7]1[CH2:38][C:10]2[N:11]([CH2:20][C:21]3[C:22]([N:27]4C(=O)C5C(=CC=CC=5)C4=O)=[N:23][CH:24]=[CH:25][CH:26]=3)[C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2].O.NN>C1COCC1.C(O)C>[CH:1]([O:4][C:5](=[O:39])[NH:6][C@@H:7]1[CH2:38][C:10]2[N:11]([CH2:20][C:21]3[C:22]([NH2:27])=[N:23][CH:24]=[CH:25][CH:26]=3)[C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 59242747(S)-{7-cyano-4-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-pyridin-3-ylmethyl]-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl}-carbamic acid isopropyl ester

Product 1

HCID 24963751(S)-[4-(2-Amino-pyridin-3-ylmethyl)-7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl esterYield 13.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Combine crude (S)-{7-cyano-4-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-pyridin-3-ylmethyl]-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl}-carbamic acid isopropyl ester (2.12 mmol, 1100 mg crude material) in a mixture of THF (22 mL) and ethanol (4 mL) and stir for 15 min. Add hydrazine hydrate 0.5 mL, 10 mmol) and stir the mixture at room temperature for 18 h. Vacuum filter the crude reaction and wash the solid with THF (50 mL). Collect the filtrate and remove the solvent under vacuum. Purify the resulting residue by silica gel chromatography (50-100% ethyl acetate/CH2Cl2) to provide 110 mg (13%) of the title compound. MS (m/z): 390 (M+1).

Workup

  1. filtrationVacuum filter the crude
  2. customreaction
  3. washwash the solid with THF (50 mL)
  4. customCollect the filtrate
  5. customremove the solvent under vacuum
  6. customPurify the resulting residue by silica gel chromatography (50-100% ethyl acetate/CH2Cl2)

Sources & evidence

ORD record
ord-a7da92ad101041b19ee5fb70af62631f
Source dataset
uspto-grants-2011_06
Patent number
US07968587B2

Reaction notes

Loading…