Ethanol → 4-(3-dimethylaminoazetidin-1-yl)-6-methoxy-N-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamine

HRID 1842808Notes

Reaction equation

HRID 1842808 reaction equation
[CH3:1][N:2]([CH3:34])[CH:3]1[CH2:6][N:5]([C:7]2[C:12]([N+:13]([O-])=O)=[CH:11][C:10]([NH:16][C:17]3[N:22]=[C:21]([C:23]4[CH:24]=[N:25][N:26]5[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=45)[CH:20]=[CH:19][N:18]=3)=[C:9]([O:32][CH3:33])[CH:8]=2)[CH2:4]1.[NH4+].[Cl-].C(O)C>[Fe].O>[CH3:34][N:2]([CH3:1])[CH:3]1[CH2:4][N:5]([C:7]2[CH:8]=[C:9]([O:32][CH3:33])[C:10]([NH:16][C:17]3[N:22]=[C:21]([C:23]4[CH:24]=[N:25][N:26]5[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=45)[CH:20]=[CH:19][N:18]=3)=[CH:11][C:12]=2[NH2:13])[CH2:6]1

Participants

6

Reactant 3

HCID 702EthanolHCID 25517Ammonium ChlorideHCID 71240790N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2×

Product 1

HCID 866773114-(3-dimethylaminoazetidin-1-yl)-6-methoxy-N-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamineYield 75.1%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 962WaterSolvent

Procedure

A mixture of N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 157, 355 mg, 0.77 mmol), iron (258 mg, 4.63 mmol), NH4Cl (30.9 mg, 0.58 mmol), ethanol (12.6 mL) and water (4.2 mL) was heated at reflux for 1.5 h. After cooling the mixture was concentrated in vacuo. The resulting residue was triturated in 10% CH3OH in CH2Cl2 (20 mL) for 15 minutes and the mixture was then filtered. The residues were triturated again with 10% CH3OH in CH2Cl2 (20 mL) and then filtered. The combined filtrates were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 0-10% methanolic ammonia in CH2Cl2 gave the title compound (249 mg, 75%) as a brown solid after trituration with diethyl ether; 1H NMR: 2.12 (6H, s), 3.02-3.09 (1H, m), 3.47 (2H, t), 3.71 (3H, s), 3.98 (2H, t), 4.04 (2H, br s), 6.28 (1H, s), 7.05 (1H, td), 7.09 (1H, s), 7.16 (1H, d), 7.36-7.41 (1H, m), 7.93 (1H, s), 8.27 (1H, d), 8.48 (1H, d), 8.74 (1H, s), 8.77 (1H, d); m/z: ES+ MH+ 431.35.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1.5 h
  3. temperatureAfter cooling the mixture
  4. concentrationwas concentrated in vacuo
  5. customThe resulting residue was triturated in 10% CH3OH in CH2Cl2 (20 mL) for 15 minutes
  6. filtrationthe mixture was then filtered
  7. customThe residues were triturated again with 10% CH3OH in CH2Cl2 (20 mL)
  8. filtrationfiltered
  9. washThe combined filtrates were washed with brine
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. customPurification by FCC
  13. washeluting with 0-10% methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-970d4c8b184f48f59bb2fa7979096e03
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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