Hydrazine → HCID 53258711, compound

HRID 1043860Notes

Reaction equation

HRID 1043860 reaction equation
[C:1]1([C:13](=O)[C:14]([C:20]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:22](C(OC(C)(C)C)=O)[CH:21]=2)(C)[C:15](OC)=[O:16])[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH2:6][CH2:5][CH2:4][N:3]3[CH:2]=1.[NH2:37][NH2:38].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C(O)(=O)C>[C:1]1([C:13]2[NH:38][NH:37][C:15](=[O:16])[C:14]=2[C:20]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[NH:22][CH:21]=2)[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH2:6][CH2:5][CH2:4][N:3]3[CH:2]=1

Participants

5

Reactant 3

HCID 9321HydrazineHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 58329567HCID 58329567, compound

Product 1

HCID 53258711HCID 53258711, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of tert-butyl 3-(1-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-3-methoxy-2-methyl-1,3-dioxopropan-2-yl)-1H-indole-1-carboxylate (6) (0.26 g, 0.52 mmol) in glacial acetic acid (2 mL) was added hydrazine (35% in H2O, 0.25 mL) followed by a catalytic amount of camphor sulfonic acid (10 mg). The reaction mixture was then microwaved at 210° C. for 10 hours. The solvent was then removed under reduced pressure and the residue partitioned between dichloromethane (10 mL) and aqueous Na2CO3 (20 mL). The organic layer was separated, dried using Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by reverse phase (HPLC, C-18) chromatography using trifluoroacetic acid as a modifier to give the desired product (7) (0.033 g, 17% yield) as a white solid. 400 MHz 1H NMR (CDCl3) δ: 11.44 (s, 1H), 11.18 (s, 1H), 7.91 (d, J=4.2 Hz, 1h), 7.6 (d, J=1.4 Hz, 1H), 7.37-7.28 (m, 2H), 7.15-7.1 (m, 1H), 7.08-6.96 (m, 2H), 6.95-6.88 (m, 1H), 6.82 (t, J=6.8 Hz, 1H), 4.08-3.88 (m, 2H), 2.9-2.78 (m, 2H), 2.08-1.96 (m, 2H), 1.82 (s, 3H); LCMS [M+H]: 369.

Workup

  1. customThe reaction mixture was then microwaved at 210° C. for 10 hours
  2. customThe solvent was then removed under reduced pressure
  3. customthe residue partitioned between dichloromethane (10 mL) and aqueous Na2CO3 (20 mL)
  4. customThe organic layer was separated
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by reverse phase (HPLC, C-18) chromatography

Sources & evidence

ORD record
ord-d98ffecc6646421aa0323173605edfd4
Source dataset
uspto-grants-2013_10
Patent number
US08563567B2

Reaction notes

Loading…