Ethanol → 4-methoxy-6-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-N'-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamine

HRID 1842799Notes

Reaction equation

HRID 1842799 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:12][C:11]3([N:16]([CH3:17])[CH2:15][CH2:14][CH2:13]3)[CH2:10]2)[C:6]([N+:18]([O-])=O)=[CH:5][C:4]=1[NH:21][C:22]1[N:27]=[C:26]([C:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]([CH3:37])[CH:29]=2)[CH:25]=[CH:24][N:23]=1.[NH4+].[Cl-].C(O)C>[Fe].O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:12][C:11]3([N:16]([CH3:17])[CH2:15][CH2:14][CH2:13]3)[CH2:10]2)[C:6]([NH2:18])=[CH:5][C:4]=1[NH:21][C:22]1[N:27]=[C:26]([C:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]([CH3:37])[CH:29]=2)[CH:25]=[CH:24][N:23]=1

Participants

6

Reactant 3

HCID 702EthanolHCID 25517Ammonium ChlorideHCID 71239536N-[2-Methoxy-4-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine2×

Product 1

HCID 866773034-methoxy-6-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-N'-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamineYield 77%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 962WaterSolvent

Procedure

A mixture of N-[2-Methoxy-4-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 147, 200 mg, 0.40 mmol), iron (134 mg, 2.40 mmol) and NH4Cl (16 mg, 0.30 mmol), ethanol (18 mL) and water (6 mL) was heated at reflux for 1 h then the mixture was allowed to cool. The mixture was then filtered and concentrated in vacuo. The resulting residue was triturated in 10% CH3OH in CH2Cl2 (15 mL) for 15 minutes and the mixture was then filtered. The residues were triturated again with 10% CH3OH in CH2Cl2 (15 mL) and the mixture then filtered. The combined filtrates were washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification by FCC, eluting with 2% 7N methanolic ammonia in CH2Cl2 gave the title compound (144 mg, 77%) as a dark green foam; 1H NMR: 1.66-1.80 (2H, m), 2.06-2.16 (2H, m), 2.42 (3H, s), 2.66 (2H, t), 3.59 (2H, d), 3.75 (3H, s), 3.83-3.91 (5H, m), 4.01 (2H, s), 6.30 (1H, s), 7.09 (1H, d), 7.16 (1H, t), 7.21-7.28 (1H, m), 7.31 (1H, s), 7.51 (1H, d), 7.70 (1H, s), 8.23 (1H, d), 8.26 (1H, s), 8.43 (1H, d); m/z: ES+ MH+ 470.7.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 h
  3. temperatureto cool
  4. filtrationThe mixture was then filtered
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was triturated in 10% CH3OH in CH2Cl2 (15 mL) for 15 minutes
  7. filtrationthe mixture was then filtered
  8. customThe residues were triturated again with 10% CH3OH in CH2Cl2 (15 mL)
  9. filtrationthe mixture then filtered
  10. washThe combined filtrates were washed with brine
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated in vacuo
  13. customPurification by FCC
  14. washeluting with 2% 7N methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-ad2a1e59dc8d4e5e907649a93fdee9e8
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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