Formamide → 2-[3-(4-Benzyl-4,7-diaza-spiro[2.5]oct-7-yl)-isoquinolin-1-yl]-acetamide

HRID 493731Notes

Reaction equation

HRID 493731 reaction equation
C(OC(=O)[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[C:8]([N:16]2[CH2:23][C:20]3([CH2:22][CH2:21]3)[N:19]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:18][CH2:17]2)[N:7]=1)C.[CH:32]([NH2:34])=[O:33].C[O-].[Na+].O>CN(C=O)C.CO.CCOC(C)=O>[CH2:24]([N:19]1[CH2:18][CH2:17][N:16]([C:8]2[N:7]=[C:6]([CH2:5][C:32]([NH2:34])=[O:33])[C:15]3[C:10]([CH:9]=2)=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH2:23][C:20]21[CH2:22][CH2:21]2)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

8

Reactant 4

HCID 713FormamideHCID 962WaterHCID 10942334Sodium MethoxideHCID 11327484[3-(4-Benzyl-4,7-diaza-spiro[2.5]oct-7-yl)-isoquinolin-1-yl]-acetic acid ethyl ester

Product 1

HCID 113611762-[3-(4-Benzyl-4,7-diaza-spiro[2.5]oct-7-yl)-isoquinolin-1-yl]-acetamide

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
105 °C

Procedure

[3-(4-Benzyl-4,7-diaza-spiro[2.5]oct-7-yl)-isoquinolin-1-yl]-acetic acid ethyl ester (700 mg, 1.68 mmol) is dissolved in dry DMF under an atmosphere of argon. Formamide (224 μl, 254 mg, 5.64 mmol) is added, and the reaction mixture is heated to 105° C. At this temperature, NaOMe (312 μl of a 5.4 M solution in MeOH, 91 mg, 1.68 mmol) is added dropwise during 20 minutes. After 30 minutes at 105° C., TLC analysis indicates complete conversion of starting material. Cooling the reaction mixture to RT is followed by addition of water and extraction with EtOAc. The organic layers are washed with H2O (twice), dried over Na2SO4 and concentrated. The residue is purified by FCC (hexanes/EtOAc 1:1 to 1:3 to 0:100 to EtOAc/MeOH 98:2) to afford the title compound. 1H NMR (DMSO, 400 MHz) δ 0.68-0.70 (m, 2H), 0.82-0.88 (m, 2H), 3.08 (t, J=4.4, 2H), 3.45 (s, 2H), 3.58 (t, J=4.4, 2H), 3.96 (s, 2H), 4.27 (s, 2H), 5.3-5.5 (br, 1H), 6.55-6.7 (br, 1H), 6.72 (s, 1H), 7.26-7.36 (m, 6H), 7.51 (t, J=8.8, 1H), 7.60 d, J=9.9, 1H), 8.02 (d, J=9.9, 1H); ES-MS: 387 [M+H]+.

Workup

  1. temperatureCooling the reaction mixture to RT
  2. washThe organic layers are washed with H2O (twice),
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue is purified by FCC (hexanes/EtOAc 1:1 to 1:3 to 0:100 to EtOAc/MeOH 98:2)

Sources & evidence

ORD record
ord-f0c177e81c5b40cdbe85c0750632f583
Source dataset
uspto-grants-2009_05
Patent number
US07534808B2

Reaction notes

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