Water → [2-(4-Amino-2,6-dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)-amine

HRID 626769Notes

Reaction equation

HRID 626769 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([Cl:11])[C:3]=1[N:12]1[CH:29]=[C:15]2[C:16]([NH:21][C:22]3[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24][N:23]=3)=[N:17][CH:18]=[C:19]([F:20])[C:14]2=[N:13]1.C1COCC1.O.[Cl-].[NH4+]>C(O)C.[Fe]>[NH2:8][C:6]1[CH:5]=[C:4]([Cl:11])[C:3]([N:12]2[CH:29]=[C:15]3[C:16]([NH:21][C:22]4[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24][N:23]=4)=[N:17][CH:18]=[C:19]([F:20])[C:14]3=[N:13]2)=[C:2]([Cl:1])[CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 25517Ammonium Chloride2×HCID 69671549[2-(2,6-Dichloro-4-nitrophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)-amine

Product 1

HCID 69671162[2-(4-Amino-2,6-dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)-amineYield 74.2%

Reagents, catalysts & solvents 2

HCID 23925IronCatalyst2×HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

[2-(2,6-Dichloro-4-nitrophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)-amine (173 mg, 0.40 mmol) was dissolved in ethanol (10 mL) and THF (4.0 mL) and water (1.0 mL) were added, followed by iron powder (325 mesh, 112 mg, 2.0 mmol) and ammonium chloride (86 mg, 1.6 mmol). The reaction mixture was heated at 70° C. for 4 hours. More iron powder (112 mg) and ammonium chloride (100 mg) were added and the mixture was heated at 70° C. for another 5 hours. The resultant mixture was cooled and filtered through Celite®. The filtrate was concentrated under reduced pressure and the residue was triturated with water. The solid obtained was dried under reduced pressure and purified by silica gel flash chromatography (0-5% methanol in DCM) to afford the title compound as an off-white solid (120 mg, 74% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.62 (s, 1H), 9.13 (d, J=2.6 Hz, 1H), 8.71 (d, J=1.2 Hz, 1H), 8.42 (s, 1H), 7.96 (d, J=3.5 Hz, 1H), 6.83 (s, 2H), 6.30 (s, 2H), 2.46 (s, 3H). LCMS (Method B): RT=3.00 min, m/z: 404 [M+H+].

Workup

  1. temperaturethe mixture was heated at 70° C. for another 5 hours
  2. filtrationfiltered through Celite®
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customthe residue was triturated with water
  5. customThe solid obtained
  6. customwas dried under reduced pressure
  7. custompurified by silica gel flash chromatography (0-5% methanol in DCM)

Sources & evidence

ORD record
ord-6fb36469282d48c78272d0eb0c92df79
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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