Water → HCID 86677246, compound

HRID 1842721Notes

Reaction equation

HRID 1842721 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[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][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[CH:14]=[C:13]([NH2:15])[C:12]([N:18]3[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]3)=[CH:11][C:10]=2[O:25][CH3:26])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 71240767HCID 71240767, compound2×

Product 1

HCID 86677246HCID 86677246, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Procedure

A mixture of 5-chloro-N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 64, 775 mg, 1.57 mmol), iron (525 mg, 9.40 mmol) and NH4Cl (62.8 mg, 1.17 mmol) was heated at reflux in ethanol (21 mL) and water (7 mL) for 2 h. The mixture was then cooled and filtered through diatomaceous earth (Celite™). The filtrate was concentrated in vacuo and then dissolved into CH2Cl2. This solution was washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 2-6% 7N methanolic ammonia in CH2Cl2 gave the title compound (480 mg, 66%) as a brown gum; 1H NMR: 2.26 (3H, s), 2.52 (4H+DMSO, m), 2.89 (4H, t), 3.68 (3H, s), 4.35 (2H, d), 6.73 (1H, s), 6.99 (1H, d), 7.13 (1H, td), 7.28-7.39 (1H, m), 8.38 (1H, d), 8.39-8.46 (2H, m), 8.82 (1H, d), 8.95 (1H, s); m/z: ES+ MH+ 465.5.

Workup

  1. temperaturewas heated
  2. temperatureThe mixture was then cooled
  3. filtrationfiltered through diatomaceous earth (Celite™)
  4. concentrationThe filtrate was concentrated in vacuo
  5. dissolutiondissolved into CH2Cl2
  6. washThis solution was washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customPurification by FCC
  10. washeluting with 2-6% 7N methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-af6bde4a72a44105aadd1963ec274177
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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