Glyoxylic acid, monohydrate → [3-((S)-7-Cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-pyridin-2-ylamino]-acetic acid

HRID 2427288Notes

Reaction equation

HRID 2427288 reaction equation
[CH:1]([O:4][C:5](=[O:29])[NH:6][C@@H:7]1[CH2:28][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].O.[C:31]([OH:35])(=[O:34])[CH:32]=O>CCO>[C:18]([C:15]1[CH:14]=[CH:13][C:12]2[N:11]([CH2:20][C:21]3[C:22]([NH:27][CH2:32][C:31]([OH:35])=[O:34])=[N:23][CH:24]=[CH:25][CH:26]=3)[C:10]3[CH2:28][C@@H:7]([NH:6][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[O:29])[CH2:8][C:9]=3[C:17]=2[CH:16]=1)#[N:19]

Participants

4

Reactant 2

HCID 15620607Glyoxylic acid, monohydrateHCID 24963751(S)-[4-(2-Amino-pyridin-3-ylmethyl)-7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester

Product 1

HCID 59242729[3-((S)-7-Cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-pyridin-2-ylamino]-acetic acidYield 65.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

Dissolve [(S)-4-(2-amino-pyridin-3-ylmethyl)-7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester (253 mg, 0.650 mmol) in EtOH (25 mL). Add 3 Å molecular sieves and glyoxylic acid monohydrate (239 mg, 2.60 mmol), then stir at 40-110° C. for 18 h under hydrogen (60 psi, 4.08 bar). Filter the reaction through a pad of diatomaceous earth and wash the catalyst/sieves with THF (50 mL). Combine the filtrate and concentrate in vacuo to a yellow oil. Triturate with water (30 mL) and sonicate the resulting aqueous slurry for 5 min. Filter off a tan solid and dry in vacuo. Triturate the solid with Et2O (5 mL) and sonicate the slurry for 30 min. Filter to obtain 190 mg (65%) of the product as a tan solid. LCMS 100% @ 3.99 min m/z 448 (M+H), 446 (M−H).

Workup

  1. filtrationFilter
  2. customthe reaction through a pad of diatomaceous earth
  3. washwash the catalyst/sieves with THF (50 mL)
  4. concentrationCombine the filtrate and concentrate in vacuo to a yellow oil
  5. customTriturate with water (30 mL)
  6. customsonicate the resulting aqueous slurry for 5 min
  7. filtrationFilter off a tan solid
  8. customdry in vacuo
  9. customTriturate the solid with Et2O (5 mL)
  10. customsonicate the slurry for 30 min
  11. filtrationFilter

Sources & evidence

ORD record
ord-2cd648205bee42eab7b9ff39906094ff
Source dataset
uspto-grants-2011_06
Patent number
US07968587B2

Reaction notes

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