Sodium Nitrite → N-[2,4-Dichloro-3-(2-methylsulfanyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl)-phenyl]-3-trifluoromethyl-benzamide

HRID 270707Notes

Reaction equation

HRID 270707 reaction equation
N[C:2]1[C:3]([C:14]2[C:15]([Cl:34])=[C:16]([NH:21][C:22](=[O:33])[C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=3)[CH:17]=[CH:18][C:19]=2[Cl:20])=[CH:4][C:5]2[CH:10]=[N:9][C:8]([S:11][CH3:12])=[N:7][C:6]=2[N:13]=1.N([O-])=[O:36].[Na+]>C(O)(C(F)(F)F)=O>[Cl:34][C:15]1[C:14]([C:3]2[C:2](=[O:36])[NH:13][C:6]3[N:7]=[C:8]([S:11][CH3:12])[N:9]=[CH:10][C:5]=3[CH:4]=2)=[C:19]([Cl:20])[CH:18]=[CH:17][C:16]=1[NH:21][C:22](=[O:33])[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:30])([F:31])[F:32])[CH:24]=1

Participants

4

Reactant 2

HCID 23668193Sodium NitriteHCID 59833927HCID 59833927, compound

Product 1

HCID 59833903N-[2,4-Dichloro-3-(2-methylsulfanyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl)-phenyl]-3-trifluoromethyl-benzamideYield 96.5%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of N-[3-(7-amino-2-methylsulfanyl-pyrido[2,3-d]pyrimidin-6-yl)-2,4-dichloro-phenyl]-3-trifluoromethyl-benzamide (1.7 g, 3.24 mmol) in TFA (15 mL) is slowly added NaNO2 (783 mg, 11.35 mmol) at 0° C. with stirring for 20 minutes. The solvents are evaporated and diluted with EtOAc and washed with saturated K2CO3, brine and water. The organic layer is dried, filtered and concentrated to give the crude product. The crude product is purified by flash silica gel column, eluting with CH2Cl2 (100%) gradient to CH2Cl2/MeOH(NH3, 2N)(93/7%), to give the title intermediate as a solid (1.64 g, 96.5%).

Workup

  1. customat 0° C.
  2. customThe solvents are evaporated
  3. additiondiluted with EtOAc
  4. washwashed with saturated K2CO3, brine and water
  5. customThe organic layer is dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product
  9. customThe crude product is purified by flash silica gel column
  10. washeluting with CH2Cl2 (100%) gradient to CH2Cl2/MeOH(NH3, 2N)(93/7%)

Sources & evidence

ORD record
ord-b096abb96db84f65af6b157797e9caf1
Source dataset
uspto-grants-2008_11
Patent number
US07449582B2

Reaction notes

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