Hydrochloric Acid → HCID 86690261, compound

HRID 80804Notes

Reaction equation

HRID 80804 reaction equation
C(O)C.[CH:4]([C:7]1[CH:11]=[C:10]([N:12]2[CH2:43][CH2:42][C:15]3[N:16]=[C:17]([C:22]4[CH:30]=[CH:29][CH:28]=[C:27]5[C:23]=4[C:24]([CH3:41])=[CH:25][N:26]5[S:31]([C:34]4[CH:40]=[CH:39][C:37]([CH3:38])=[CH:36][CH:35]=4)(=[O:33])=[O:32])[N:18]=[C:19](OC)[C:14]=3[CH2:13]2)[N:9]([CH3:44])[N:8]=1)([CH3:6])[CH3:5].[ClH:45].C(=O)(O)[O-].[Na+]>ClCCl>[Cl:45][C:19]1[C:14]2[CH2:13][N:12]([C:10]3[N:9]([CH3:44])[N:8]=[C:7]([CH:4]([CH3:5])[CH3:6])[CH:11]=3)[CH2:43][CH2:42][C:15]=2[N:16]=[C:17]([C:22]2[CH:30]=[CH:29][CH:28]=[C:27]3[C:23]=2[C:24]([CH3:41])=[CH:25][N:26]3[S:31]([C:34]2[CH:35]=[CH:36][C:37]([CH3:38])=[CH:39][CH:40]=2)(=[O:32])=[O:33])[N:18]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 516892Sodium BicarbonateHCID 712405966-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Product 1

HCID 86690261HCID 86690261, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
87 °C

Procedure

Ethanol (1.8 mL) was added to 6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (195 mg, 0.342 mmol) followed by 12 N aqueous hydrochloric acid (1.8 mL, 21.8 mmol). The mixture was then heated to 87° C. for ca. 15 hours. The mixture was then cooled to room temperature, diluted with dichloromethane, and slowly neutralized with saturated aqueous sodium bicarbonate. The resulting layers were separated and the aqueous layers were extracted an additional time with dichloromethane. The organic layers were combined and dried by passing through a phase separator and then concentrated. The resulting residue was diluted with 1,2-dichloroethane (3.5 mL) and place at 0° C. Then N-chloromethylene-N,N-dimethyl ammonium chloride (Vilsmeier reagent) (85 mg, 067 mmol) was added. The resulting mixture was then heated to 35° C. After 5 minutes at 35° C. the mixture was diluted with dichloromethane, and slowly neutralized with saturated aqueous sodium bicarbonate. The resulting layers were separated and the aqueous layers were extracted an additional time with dichloromethane. The organic layers were combined and dried over Na2SO4, filtered and concentrated to furnish 4-chloro-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine without the need for further purification. MS (ESI+) m/z 575.3 (M+H)+.

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. customThe resulting layers were separated
  3. extractionthe aqueous layers were extracted an additional time with dichloromethane
  4. customdried
  5. concentrationconcentrated
  6. additionThe resulting residue was diluted with 1,2-dichloroethane (3.5 mL) and place at 0° C
  7. additionThen N-chloromethylene-N,N-dimethyl ammonium chloride (Vilsmeier reagent) (85 mg, 067 mmol) was added
  8. temperatureThe resulting mixture was then heated to 35° C
  9. additionAfter 5 minutes at 35° C. the mixture was diluted with dichloromethane
  10. customThe resulting layers were separated
  11. extractionthe aqueous layers were extracted an additional time with dichloromethane
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-6d404f8594a941edbeca7b2d0a6084a2
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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