Water → 4-(4-chloro-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-3,5-dimethyl-1H-indazole-1-carbaldehyde

HRID 80851Notes

Reaction equation

HRID 80851 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH3:32])[C:9]=2[C:11]2[N:12]=[C:13](O)[C:14]3[CH2:20][N:19]([C:21]4[CH:26]=[C:25]([CH:27]([CH3:29])[CH3:28])[CH:24]=[CH:23][C:22]=4[CH3:30])[CH2:18][CH2:17][C:15]=3[N:16]=2)[NH:4][N:3]=1.[CH3:33][N+](C)=C[Cl:36].[Cl-:38].[OH2:39]>ClCCCl>[Cl:36][C:13]1[C:14]2[CH2:20][N:19]([C:21]3[CH:26]=[C:25]([CH:27]([CH3:29])[CH3:28])[CH:24]=[CH:23][C:22]=3[CH3:30])[CH2:18][CH2:17][C:15]=2[N:16]=[C:11]([C:9]2[C:8]([CH3:32])=[CH:7][CH:6]=[C:5]3[C:10]=2[C:2]([CH3:1])=[N:3][NH:4]3)[N:12]=1.[Cl:38][C:13]1[C:14]2[CH2:20][N:19]([C:21]3[CH:26]=[C:25]([CH:27]([CH3:28])[CH3:29])[CH:24]=[CH:23][C:22]=3[CH3:30])[CH2:18][CH2:17][C:15]=2[N:16]=[C:11]([C:9]2[C:8]([CH3:32])=[CH:7][CH:6]=[C:5]3[C:10]=2[C:2]([CH3:1])=[N:3][N:4]3[CH:33]=[O:39])[N:12]=1

Participants

6

Reactant 3

HCID 962WaterHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 178424912HCID 178424912, compound

Product 2

HCID 866902884-(4-chloro-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-3,5-dimethyl-1H-indazole-1-carbaldehydeHCID 178424910HCID 178424910, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 2-(3,5-dimethyl-1H-indazol-4-yl)-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-ol (1.3 g, 3.04 mmol) in DCE (50 mL) was added Vilsmeier reagent (1.95 g, 15.2 mmol). The mixture was heated at 50° C. for 2 h. LC-MS showed reaction complete. The reaction mixture was poured into water, and the layers were separated. The aqueous layer was extracted with DCM. The organics were combined and concentrated. The residue was purified by FCC (0-100% EtOAc/heptane) to provide 4-chloro-2-(3,5-dimethyl-1H-indazol-4-yl)-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine MS (ESI+) m/z 446.3 (M+H)+ and 4-(4-chloro-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-3,5-dimethyl-1H-indazole-1-carbaldehyde MS (ESE) m/z 474.3 (M+H)+.

Workup

  1. customreaction complete
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with DCM
  4. concentrationconcentrated
  5. customThe residue was purified by FCC (0-100% EtOAc/heptane)

Sources & evidence

ORD record
ord-cd341f6566c64530a0ac3e7817106fd5
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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