Hydrochloric Acid → N-{3-[3-(2-{[2-(Dimethylamino)-2,3-dihydro-1H-inden-5-yl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide

HRID 1159977Notes

Reaction equation

HRID 1159977 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[C:19]([NH:23][C:24](=[O:33])[C:25]4[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=4[F:32])[CH:20]=[CH:21][CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.[NH2:34][C:35]1[CH:36]=[C:37]2[C:41](=[CH:42][CH:43]=1)[CH2:40][CH:39]([N:44]([CH3:46])[CH3:45])[CH2:38]2.Cl>C(O)(C)C>[CH3:45][N:44]([CH3:46])[CH:39]1[CH2:38][C:37]2[C:41](=[CH:42][CH:43]=[C:35]([NH:34][C:2]3[N:7]=[C:6]([C:8]4[C:9]([C:17]5[CH:18]=[C:19]([NH:23][C:24](=[O:33])[C:25]6[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=6[F:32])[CH:20]=[CH:21][CH:22]=5)=[N:10][N:11]5[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=45)[CH:5]=[CH:4][N:3]=3)[CH:36]=2)[CH2:40]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 54309634HCID 54309634, compoundHCID 59513803N-{3-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide

Product 1

HCID 11512754N-{3-[3-(2-{[2-(Dimethylamino)-2,3-dihydro-1H-inden-5-yl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
180 °C

Procedure

The title compound was synthesized by combining N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide (152 mg, 0.33 mmol), (5-amino-2,3-dihydro-1H-inden-2-yl)dimethylamine (70 mg, 0.40 mmol), hydrochloric acid (0.033 mmol, 33 uL 1M HCl/diethylether) and 3 mL isopropanol in a sealed vessel. The vial and contents were heated at 180° C. for 30 mins. The reaction was cooled and concentrated. The residue was partitioned between EtOAc and saturated aqueous NaHCO3. The organic layer was washed with brine, dried with MgSO4 and concentrated. The crude material was purified by silica gel column chromatography (0-100% gradient; (90% CH2Cl2:9% MeOH:1% NH4OH/CH2Cl2)) Purification provided 28 mg (14%) of the coupled adduct. ESIMS (M+H)+=603.30.

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated
  3. customThe residue was partitioned between EtOAc and saturated aqueous NaHCO3
  4. washThe organic layer was washed with brine
  5. dry with materialdried with MgSO4
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel column chromatography (0-100% gradient; (90% CH2Cl2:9% MeOH:1% NH4OH/CH2Cl2)) Purification

Sources & evidence

ORD record
ord-69adfef412014f61b7ea4239c48ce3bb
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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