Ammonium Chloride → HCID 86677341, compound

HRID 1842759Notes

Reaction equation

HRID 1842759 reaction equation
[NH4+].[Cl-].[Cl:3][C:4]1[C:5]([C:32]2[CH:33]=[N:34][N:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=23)=[N:6][C:7]([NH:10][C:11]2[CH:16]=[C:15]([N+:17]([O-])=O)[C:14]([N:20]([CH3:29])[CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)=[CH:13][C:12]=2[O:30][CH3:31])=[N:8][CH:9]=1>O.C(O)C.[Fe]>[Cl:3][C:4]1[C:5]([C:32]2[CH:33]=[N:34][N:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=23)=[N:6][C:7]([NH:10][C:11]2[CH:16]=[C:15]([NH2:17])[C:14]([N:20]([CH3:29])[CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)=[CH:13][C:12]=2[O:30][CH3:31])=[N:8][CH:9]=1

Participants

6

Reactant 2

HCID 25517Ammonium Chloride2×HCID 71270301HCID 71270301, compound2×

Product 1

HCID 86677341HCID 86677341, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 23925IronCatalyst2×HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A solution of NH4Cl (28.1 mg, 0.53 mmol) in water (13.00 mL) was added in one portion to a stirred mixture of N-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-2-methoxy-N′-methyl-N′-(2-morpholin-4-ylethyl)-5-nitrobenzene-1,4-diamine (Intermediate 106, 426 mg, 0.75 mmol) and iron (251 mg, 4.50 mmol) in ethanol (39 mL). The resulting mixture was stirred at reflux for 2 h. Further iron (251 mg, 4.50 mmol) and NH4Cl (28.1 mg, 0.53 mmol) was added and the mixture was stirred at reflux for a further 0.5 h. The mixture was concentrated in vacuo and the residue was mixed with DMF (5 mL) and then purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M methanolic ammonia in CH2Cl2 and appropriate fractions were combined and concentrated in vacuo. Purification by FCC, eluting with 1.5-7% 2M methanolic ammonia in CH2Cl2 gave the title compound (304 mg, 80%) as a yellow foam; 1H NMR: 2.43 (4H, m), 2.45 (2H, t), 2.68 (3H, s), 2.93 (2H, t), 3.51-3.61 (4H, m), 3.66 (3H, s), 4.73 (2H, s), 6.77 (1H, s), 6.90 (1H, s), 7.12 (1H, m), 7.34 (1H, m), 8.37 (1H, s), 8.43 (1H, d), 8.49 (1H, s), 8.84 (1H, d), 8.95 (1H, s); m/z: ES+ MH+ 509.

Workup

  1. temperatureat reflux for 2 h
  2. stirringthe mixture was stirred
  3. temperatureat reflux for a further 0.5 h
  4. concentrationThe mixture was concentrated in vacuo
  5. additionthe residue was mixed with DMF (5 mL)
  6. custompurified by ion exchange chromatography
  7. washThe desired product was eluted from the column
  8. concentrationconcentrated in vacuo
  9. customPurification by FCC
  10. washeluting with 1.5-7% 2M methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-06d718629a7444a9bfea9abb79de1896
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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