Water → N-(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-4-(3-dimethylaminoazetidin-1-yl)-6-methoxybenzene-1,3-diamine

HRID 1842691Notes

Reaction equation

HRID 1842691 reaction equation
[Cl:1][C:2]1[C:3]([C:27]2[CH:28]=[N:29][N:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=23)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([N+:15]([O-])=O)[C:12]([N:18]3[CH2:21][CH:20]([N:22]([CH3:24])[CH3:23])[CH2:19]3)=[CH:11][C:10]=2[O:25][CH3:26])=[N:6][CH:7]=1.[NH4+].[Cl-].O>C(O)C.[Fe]>[Cl:1][C:2]1[C:3]([C:27]2[CH:28]=[N:29][N:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=23)=[N:4][C:5]([NH:8][C:9]2[C:10]([O:25][CH3:26])=[CH:11][C:12]([N:18]3[CH2:21][CH:20]([N:22]([CH3:24])[CH3:23])[CH2:19]3)=[C:13]([NH2:15])[CH:14]=2)=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 712407235-chloro-N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2×

Product 1

HCID 86677329N-(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-4-(3-dimethylaminoazetidin-1-yl)-6-methoxybenzene-1,3-diamineYield 94%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Procedure

A mixture of 5-chloro-N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 25, 265 mg, 0.54 mmol), iron (179 mg, 3.21 mmol) and NH4Cl (20.05 mg, 0.37 mmol) was heated at reflux in ethanol (6 mL) and water (2 mL) for 1 h. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M methanolic ammonia and appropriate fractions were concentrated in vacuo to give the title compound (235 mg, 94%) as a yellow solid which was used without further purification; 1H NMR: 2.13 (6H, s), 3.07 (1H, s), 3.50 (2H, t), 3.66 (3H, s), 4.00 (3H, t), 4.05 (2H, s), 6.28 (1H, s), 6.79 (1H, s), 7.10 (1H, t), 7.3-7.39 (1H, m), 8.33 (1H, s), 8.37 (1H, s), 8.80 (1H, d), 8.93 (1H, s); m/z: ES+ MH+ 465.25.

Workup

  1. temperaturewas heated
  2. customThe crude product was purified by ion exchange chromatography
  3. washThe desired product was eluted from the column
  4. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-ce127545f62c4da3a7065d33d23c8676
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

Loading…