Formamide → 3-[3-(4,7-Diaza-spiro[2.5]oct-7-yl)-naphthalen-1-yl]-4-(1-methyl-1H-indol-3-yl)-pyrrole-2,5-dione

HRID 493729Notes

Reaction equation

HRID 493729 reaction equation
C(O[C:4](=[O:31])[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](CC3C=CC=CC=3)[CH2:18][CH2:17]2)[CH:7]=1)C.C(N1CCN(C2[CH:48]=[C:49]([CH2:57][C:58]([NH2:60])=[O:59])[C:50]3[C:55](C=2)=[CH:54][CH:53]=[CH:52][CH:51]=3)CC21CC2)C1C=CC=CC=1.[CH:61]([NH2:63])=O.C[O-].[Na+]>CN(C=O)C.CO>[CH2:21]1[C:20]2([CH2:23][N:16]([C:8]3[CH:7]=[C:6]([C:5]4[C:4](=[O:31])[NH:60][C:58](=[O:59])[C:57]=4[C:49]4[C:50]5[C:55](=[CH:54][CH:53]=[CH:52][CH:51]=5)[N:63]([CH3:61])[CH:48]=4)[C:15]4[C:10]([CH:9]=3)=[CH:11][CH:12]=[CH:13][CH:14]=4)[CH2:17][CH2:18][NH:19]2)[CH2:22]1

Participants

6

Reactant 3

HCID 713FormamideHCID 10942334Sodium MethoxideHCID 865983552-[3-(4-Benzyl-4,7-diaza-spiro[2.5] oct-7-yl)-naphthalen-1-yl]-acetamide [3-(4-Benzyl-4,7-diaza-spiro[2.5] oct-7-yl)-naphthalen-1-yl]-acetic acid ethyl ester

Product 1

HCID 211145053-[3-(4,7-Diaza-spiro[2.5]oct-7-yl)-naphthalen-1-yl]-4-(1-methyl-1H-indol-3-yl)-pyrrole-2,5-dione

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
105 °C

Procedure

2-[3-(4-Benzyl-4,7-diaza-spiro[2.5]oct-7-yl)-naphthalen-1-yl]-acetamide [3-(4-Benzyl-4,7-diaza-spiro[2.5]oct-7-yl)-naphthalen-1-yl]-acetic acid ethyl ester (347 mg, 0.84 mmol) and formamide (126 mg, 2.80 mmol) are dissolved under an atmosphere of argon in DMF (1 ml). The solution is heated to 105° C., and NaOMe (155 μL of a 5.4 M solution in MeOH, 45 mg, 0.84 mmol) is added dropwise during 15 minutes. After 30 minutes at 105° C., TLC analysis indicates complete consumption of starting material. The reaction mixture is cooled to RT, diluted with water, and extracted with EtOAc. The EtOAc layers are washed twice with water. Removal of solvent and purification by FCC (EtOAc/MeOH 98:2 to 96:4 to 90:10) yielded the title compound. 1H NMR (CDCl3, 400 MHz) δ 0.71 (ddd, 2H), 0.89 (ddd, 2H), 3.10 (ddd, 2H), 3.16 (s, 2H), 3.31 (ddd, 2H), 3.93 (s, 2H), 3.99 (s, 2H), 5.33 (br, 1H), 5.42 (br, 1H), 7.11 (s, 1H), 7.23 (d, J=2.0, 1H), 7.32 (m, 5H), 7.37 (dd, J=6.7 Hz, 1H), 7.45 (dd, J=6.7 Hz, 1H), 7.73 (d, J=8.9 Hz, 1H), 7.85 (d, J=8.9 Hz, 1H); ES-MS: 386 [M+H]+.

Workup

  1. customconsumption of starting material
  2. temperatureThe reaction mixture is cooled to RT
  3. additiondiluted with water
  4. extractionextracted with EtOAc
  5. washThe EtOAc layers are washed twice with water
  6. customRemoval of solvent and purification by FCC (EtOAc/MeOH 98:2 to 96:4 to 90:10)

Sources & evidence

ORD record
ord-0cf66559c6f040d8aa49f964ef66de3b
Source dataset
uspto-grants-2009_05
Patent number
US07534808B2

Reaction notes

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