Sodium Nitrite → HCID 57761731, compound

HRID 230955Notes

Reaction equation

HRID 230955 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]=[C:13]([N:15]3[CH2:19][CH2:18][CH2:17][CH:16]3[CH3:20])[N:12]=[C:11]([N:21]3[CH2:26][CH2:25][N:24]([C:27]4[N:32]=[CH:31][C:30](N)=[CH:29][C:28]=4[CH3:34])[CH2:23][CH2:22]3)[CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].N([O-])=[O:36].[Na+]>OS(O)(=O)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]=[C:13]([N:15]3[CH2:19][CH2:18][CH2:17][CH:16]3[CH3:20])[N:12]=[C:11]([N:21]3[CH2:26][CH2:25][N:24]([C:27]4[N:32]=[CH:31][C:30]([OH:36])=[CH:29][C:28]=4[CH3:34])[CH2:23][CH2:22]3)[CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 2

HCID 23668193Sodium NitriteHCID 57761684HCID 57761684, compound

Product 1

HCID 57761731HCID 57761731, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1118Sulfuric AcidSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled solution of 6-{4-[6-(3-chloro-4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-piperazin-1-yl}-5-methyl-pyridin-3-ylamine (146 mg, 0.303 mmol) in 10% aqueous H2SO4 add NaNO2 (22 mg, 0.318 mmol) in 1 ml of water, dropwise. Stir the solution at 0° C. for 30 minutes. Heat the mixture at 90° C. for 1 hour. Cool to room temperature, adjust the pH to 7, and extract with EtOAc. Wash with brine, dry the solution (Na2SO4), and concentrate under reduced pressure. Purify the residue by flash column chromatography eluting with EtOAc:Hexanes (1:1) to afford 6-{4-[6-(3-chloro-4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-piperazin-1-yl}-5-methyl-pyridin-3-ol as an off white solid. 1H NMR (300 MHz, CDCl3): δ1.29 (t, 3H, J=6.3 Hz, CH3); 1.69 (m, 1H, CH2CH2); 1.90 (m, 1H, CH2CH2); 2.05 (m, 2H, CH2CH2); 2.29 (s, 3H, Ar—CH3); 3.11 (m, 4H); 3.67 (m, 4H); 3.78 (m, 4H); 4.35 (m, 1H); 6.23 (s, 1H, Ar—H); 7.03 (d, J=2.4 Hz, 1H); 7.16 (m, 1H); 7.72 (d, 1H, J=2.7 Hz); 7.86 (m, 1H); 8.04 (m, 1H).

Workup

  1. temperatureHeat the mixture at 90° C. for 1 hour
  2. temperatureCool to room temperature
  3. extractionextract with EtOAc
  4. washWash with brine
  5. dry with materialdry the solution (Na2SO4)
  6. concentrationconcentrate under reduced pressure
  7. customPurify the residue by flash column chromatography
  8. washeluting with EtOAc:Hexanes (1:1)

Sources & evidence

ORD record
ord-b95f6517958a4015aa74707424ed030b
Source dataset
uspto-grants-2009_07
Patent number
US07566712B2

Reaction notes

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