Hydrochloric Acid → 6-(4-chloro-3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-(3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

HRID 80806Notes

Reaction equation

HRID 80806 reaction equation
Cl[C:2]1[C:3]2[CH2:31][N:30]([C:32]3[N:36]([CH3:37])[N:35]=[C:34]([CH:38]([CH3:40])[CH3:39])[C:33]=3[Cl:41])[CH2:29][CH2:28][C:4]=2[N:5]=[C:6]([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[C:10]([CH3:27])=[CH:11][N:12]3[S:17]([C:20]2[CH:26]=[CH:25][C:23]([CH3:24])=[CH:22][CH:21]=2)(=[O:19])=[O:18])[N:7]=1.C(N(C(C)C)CC)(C)C.Cl.[CH3:52][C:53]1([CH3:59])[CH2:58][CH2:57][CH2:56][NH:55][CH2:54]1>ClCCl.[Cl-].[Na+].O.C(O)(C)C>[Cl:41][C:33]1[C:34]([CH:38]([CH3:40])[CH3:39])=[N:35][N:36]([CH3:37])[C:32]=1[N:30]1[CH2:29][CH2:28][C:4]2[N:5]=[C:6]([C:8]3[CH:16]=[CH:15][CH:14]=[C:13]4[C:9]=3[C:10]([CH3:27])=[CH:11][N:12]4[S:17]([C:20]3[CH:21]=[CH:22][C:23]([CH3:24])=[CH:25][CH:26]=3)(=[O:18])=[O:19])[N:7]=[C:2]([N:55]3[CH2:56][CH2:57][CH2:58][C:53]([CH3:59])([CH3:52])[CH2:54]3)[C:3]=2[CH2:31]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 709423,3-DimethylpiperidineHCID 81531DiisopropylethylamineHCID 866902624-chloro-6-(4-chloro-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

Product 1

HCID 712405676-(4-chloro-3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-(3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
120 °C

Procedure

Isopropanol (2.2 mL) was added to 4-chloro-6-(4-chloro-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 (85 mg, 0.139 mmol) in a microwave vial. Then diisopropylethylamine (0.1 mL, 0.573 mmol) was added followed by the HCl salt of 3,3-dimethylpiperidine (25 mg, 0.167 mmol). The vessel was sealed and heated via microwave irradiation at 120° C. for 2.5 h then cooled to room temperature and diluted with dichloromethane and brine. The layers were separated and the organic layer was dried over Na2SO4, filtered, and concentrated. The resulting residue was purified via silica gel flash chromatography (25-55% ethyl acetate/heptanes) to provide 6-(4-chloro-3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-(3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. MS (ESI+) m/z 686.4 (M+H)+.

Workup

  1. customThe vessel was sealed
  2. temperaturethen cooled to room temperature
  3. customThe layers were separated
  4. dry with materialthe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified via silica gel flash chromatography (25-55% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-2343c1545aff4d4080979a7173178063
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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