Diisopropylethylamine → 5-chloro-N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine

HRID 1842692Notes

Reaction equation

HRID 1842692 reaction equation
CCN(C(C)C)C(C)C.[Cl:10][C:11]1[C:12]([C:30]2[CH:31]=[N:32][N:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=23)=[N:13][C:14]([NH:17][C:18]2[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[C:21](F)=[CH:20][C:19]=2[O:28][CH3:29])=[N:15][CH:16]=1.Cl.Cl.[CH3:41][N:42]([CH3:47])[CH:43]1[CH2:46][NH:45][CH2:44]1.CN(C)C1CNC1>CC(N(C)C)=O>[Cl:10][C:11]1[C:12]([C:30]2[CH:31]=[N:32][N:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=23)=[N:13][C:14]([NH:17][C:18]2[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[C:21]([N:45]3[CH2:46][CH:43]([N:42]([CH3:47])[CH3:41])[CH2:44]3)=[CH:20][C:19]=2[O:28][CH3:29])=[N:15][CH:16]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 10351656N,N-dimethylazetidin-3-amineHCID 22121220N,N-dimethylazetidin-3-amine dihydrochloride2×HCID 712393485-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2×

Product 1

HCID 712407235-chloro-N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amineYield 102.7%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

DIPEA (0.341 mL, 1.96 mmol) was added to a mixture of 5-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(pyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine (Intermediate 20, 254 mg, 0.61 mmol) and N,N-dimethylazetidin-3-amine dihydrochloride (Intermediate 26, 106 mg, 0.61 mmol) in DMA (4 mL) and the mixture was heated to 100° C. for 0.5 h. Further N,N-dimethylazetidin-3-amine (35 mg, 0.19 mmol) was then added and the mixture was heated at 100° C. for a further 2 h and was then left at r.t. overnight. The mixture was purified directly by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M methanolic ammonia and was concentrated in vacuo onto silica. Purification by FCC, eluting with 0-4% 7N methanolic ammonia in CH2Cl2 gave the title compound (310 mg, 102%) as an orange solid, which was used without further purification; 1H NMR: 2.14 (6H, s), 3.08-3.18 (1H, m), 3.76 (2H, dd), 3.89 (3H, s), 4.02-4.11 (2H, m), 6.28 (1H, s), 7.12 (1H, td), 7.30-7.39 (1H, m), 8.12 (1H, s), 8.37 (1H, br s), 8.42 (1H, s), 8.68 (1H, s), 8.83 (1H, d), 8.94 (1H, d); m/z: ES+ MH+ 495.56.

Workup

  1. temperaturethe mixture was heated at 100° C. for a further 2 h
  2. customThe mixture was purified directly by ion exchange chromatography
  3. washThe desired product was eluted from the column
  4. concentrationwas concentrated in vacuo onto silica
  5. customPurification by FCC
  6. washeluting with 0-4% 7N methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-20cd47f792db44a6a7f0e1923b52dd8d
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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