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

HRID 1842708Notes

Reaction equation

HRID 1842708 reaction equation
[Cl:1][C:2]1[C:3]([C:29]2[CH:30]=[N:31][N:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=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][C:20]4([CH2:25][CH2:24][CH2:23][N:22]4[CH3:26])[CH2:19]3)=[CH:11][C:10]=2[O:27][CH3:28])=[N:6][CH:7]=1.[NH4+].[Cl-].O>C(O)C.[Fe]>[Cl:1][C:2]1[C:3]([C:29]2[CH:30]=[N:31][N:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=23)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([NH2:15])[C:12]([N:18]3[CH2:19][C:20]4([CH2:25][CH2:24][CH2:23][N:22]4[CH3:26])[CH2:21]3)=[CH:11][C:10]=2[O:27][CH3:28])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 712407855-chloro-N-[2-methoxy-4-(5-methyl-2,5-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2×

Product 1

HCID 86677239N'-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-4-methoxy-6-(5-methyl-2,5-diazaspiro[3.4]octan-2-yl)benzene-1,3-diamineYield 34%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Procedure

A mixture of 5-chloro-N-[2-methoxy-4-(5-methyl-2,5-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 46, 95 mg, 0.18 mmol), iron (61 mg, 1.09 mmol) and NH4Cl (7.32 mg, 0.14 mmol) was heated at reflux in ethanol (10.5 mL) and water (3.5 mL) for 2 h. The mixture was cooled and filtered through diatomaceous earth (Celite™). The filtrate was concentrated in vacuo and the residue was dissolved in CH2Cl2. This solution was washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification by FCC, eluting with 2-6% 7N methanolic ammonia in CH2Cl2 gave the title compound (30 mg, 34%) as a brown gum; m/z: ES+ MH+ 491.5.

Workup

  1. temperaturewas heated
  2. temperatureThe mixture was cooled
  3. filtrationfiltered through diatomaceous earth (Celite™)
  4. concentrationThe filtrate was concentrated in vacuo
  5. dissolutionthe residue was dissolved in CH2Cl2
  6. washThis solution was washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customPurification by FCC
  10. washeluting with 2-6% 7N methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-0c40728fc4d8420eb125881a7589bdca
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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