Ethanol → 4-methoxy-6-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-N'-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamine

HRID 1842814Notes

Reaction equation

HRID 1842814 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[CH:29]=[N:30][N:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=23)[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[CH2:10][C:11]3([N:16]([CH3:17])[CH2:15][CH2:14][CH2:13]3)[CH2:12]2)[C:6]([NH2:18])=[CH:5][C:4]=1[NH:21][C:22]1[N:27]=[C:26]([C:28]2[CH:29]=[N:30][N:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=23)[CH:25]=[CH:24][N:23]=1

Participants

6

Reactant 3

HCID 702EthanolHCID 25517Ammonium ChlorideHCID 71240856N-[2-methoxy-4-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2×

Product 1

HCID 866773174-methoxy-6-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-N'-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamineYield 89.2%

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-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 163, 404 mg, 0.83 mmol), iron (278 mg, 4.98 mmol), NH4Cl (33.3 mg, 0.62 mmol), ethanol (15 mL) and water (5 mL) was heated at reflux for 1.5 h. After cooling, the mixture was filtered and the residues were washed with 1:10 CH3OH—CH2Cl2 (20 mL). The combined filtrates were concentrated in vacuo onto silica. Purification by FCC, eluting with 1-10% methanolic ammonia in CH2Cl2 gave the title compound (338 mg, 89%) as a yellow solid; 1H NMR: 1.72 (2H, dt), 2.11 (2H, dd), 2.42 (3H, s), 2.66 (2H, t), 3.63 (2H, d), 3.72 (3H, s), 3.87 (2H, d), 4.03 (2H, s), 6.29 (1H, s), 7.06 (1H, td), 7.10 (1H, s), 7.16 (1H, d), 7.35-7.42 (1H, m), 7.93 (1H, s), 8.27 (1H, d), 8.52 (1H, d), 8.74 (1H, s), 8.77 (1H, t); m/z: ES+ MH+ 457.36.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1.5 h
  3. temperatureAfter cooling
  4. filtrationthe mixture was filtered
  5. washthe residues were washed with 1:10 CH3OH—CH2Cl2 (20 mL)
  6. concentrationThe combined filtrates were concentrated in vacuo onto silica
  7. customPurification by FCC
  8. washeluting with 1-10% methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-12a09bd2840d4612a52ad5415604e021
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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