N-methyl-2-pyrrolidone → HCID 59242734, compound

HRID 2427287Notes

Reaction equation

HRID 2427287 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:26](Cl)=[N:25][CH:24]=[CH:23][N:22]=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].C[N:31]1C(=O)CCC1>>[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:26]([NH2:31])=[N:25][CH:24]=[CH:23][N:22]=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

3

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 86640058HCID 86640058, compound

Product 1

HCID 59242734HCID 59242734, compoundYield 18%

Conditions

Temperature
0 °C

Procedure

Dissolve (S)-[4-(3-chloro-pyrazin-2-ylmethyl)-7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester (8.89 g, 21.7 mmol) in NMP (36 mL) and distribute the mixture evenly between three 10-20 mL microwave reactor vials. Cool each reaction vessel to 0° C. and sparge with anhydrous NH3 for 15 min. Seal each vessel and heat to 200° C. for 1 h in a microwave reactor. Combine the reaction mixtures together in water (500 mL) and sonicate for 20 min. Filter off a tan solid, then dissolve the solid in EtOAc (500 mL). Dry the organics (MgSO4), filter, and concentrate to a volume of 10 mL. Dilute the organics with MeOH (20 mL) and CH2Cl2 (10 mL) and absorb onto silica gel in vacuo. Purify on silica gel (340 g) using 1-10% (2 M NH3/MeOH)/(1:1 CH2Cl2/hexanes) to afford 1.50 g (18%) of the title compound as a yellow solid. MS (m/z) 391 (M+1), 389 (M−1). Pool and concentrate fractions containing impure product (1.2 g), and re-purify on silica gel (80 g) using 3-8% (2 M NH3/MeOH)/(1:1 CH2Cl2/hexanes) to afford a second crop (503 mg, 6%) of the title compound as a yellow solid.

Workup

  1. customsparge with anhydrous NH3 for 15 min
  2. customSeal each vessel
  3. temperatureheat to 200° C. for 1 h in a microwave reactor
  4. customthe reaction mixtures together in water (500 mL)
  5. customsonicate for 20 min
  6. filtrationFilter off a tan solid
  7. dissolutiondissolve the solid in EtOAc (500 mL)
  8. dry with materialDry the organics (MgSO4)
  9. filtrationfilter
  10. concentrationconcentrate to a volume of 10 mL
  11. additionDilute the organics with MeOH (20 mL) and CH2Cl2 (10 mL)
  12. customabsorb onto silica gel in vacuo
  13. customPurify on silica gel (340 g)

Sources & evidence

ORD record
ord-6cb8efb4f27646caab710be1d61ca4be
Source dataset
uspto-grants-2011_06
Patent number
US07968587B2

Reaction notes

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