HCID 15063398, compound → HCID 15063399, compound

HRID 510019Notes

Reaction equation

HRID 510019 reaction equation
[H][H].[O:3]=[C:4]1[CH:16](C(OC(C)(C)C)=O)[N:8]2[C:9]3[C:14]([CH:15]=[C:7]2[CH2:6][CH2:5]1)=[CH:13][CH:12]=[CH:11][CH:10]=3>C1(C)C=CC=CC=1>[CH:13]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:14]=1[CH:15]=[C:7]1[CH2:6][CH2:5][C:4](=[O:3])[CH2:16][N:8]12

Participants

4

Reactant 2

HCID 15063398HCID 15063398, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 15063399HCID 15063399, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Compounds of formula (I) wherein R3 represents hydrogen may be prepared from the respective tert-butyl 7-oxo-6,7,8,9-tetrahydropyrido[1,2-a]indole-6-carboxylate derivatives (5). Decarboxylation by reaction with silica gel in an aprotic solvent such as toluene gives the corresponding 8,9-dihydropyrido[1,2-a]indol-7(6H)-one derivatives (9). Reductive amination with ammonium acetate in the presence of a reducing agent such as NaBH3CN in a mixture of AcOH and EtOH and subsequent Boc protection yields the corresponding tert-butyl (6,7,8,9-tetrahydropyrido[1,2-a]indol-7-yl)carbamate derivatives (10). Friedel-Craft acylation by reaction with oxalyl chloride in an aprotic solvent such as DCM, followed by esterification with MeOH and subsequent reduction with triethylsilane in the presence of TFA gives the corresponding methyl 2-(7-amino-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)acetate (11). Reaction with an appropriate heteroaryl halide like R4—Cl in the presence of a base such as K2CO3 in an aprotic solvent such as DMA and subsequent saponification with a base such as NaOH furnished the compounds of formula (I).

Sources & evidence

ORD record
ord-41e988b7e43c426aa8502dfd1aabbd58
Source dataset
uspto-grants-2015_08
Patent number
US09096595B2

Reaction notes

Loading…