HCID 59511436, compound → HCID 59513765, compound

HRID 1159994Notes

Reaction equation

HRID 1159994 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]([CH2:41][N:42]([CH2:49][CH2:50][N:51]([CH3:53])[CH3:52])C(=O)C(F)(F)F)[CH:38]=[CH:39][CH:40]=1>CC(O)C.Cl.C(Cl)Cl.CO>[CH3:52][N:51]([CH3:53])[CH2:50][CH2:49][NH:42][CH2:41][C:37]1[CH:36]=[C:35]([NH:34][C:2]2[N:7]=[C:6]([C:8]3[C:9]([C:17]4[CH:18]=[C:19]([NH:23][C:24](=[O:33])[C:25]5[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=5[F:32])[CH:20]=[CH:21][CH:22]=4)=[N:10][N:11]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=34)[CH:5]=[CH:4][N:3]=2)[CH:40]=[CH:39][CH:38]=1

Participants

7

Reactant 2

HCID 59511436HCID 59511436, compoundHCID 59513803N-{3-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide

Product 1

HCID 59513765HCID 59513765, compoundYield 24.2%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidCatalystHCID 887MethanolSolventHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
180 °C

Procedure

To a suspension of N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide (75 mg, 0.16 mmol) (prepared according to a procedure similar to that described in Example 27, Step C) and N-[(3-aminophenyl)methyl]-N-[2-(dimethylamino)ethyl]-2,2,2-trifluoroacetamide (58 mg, 0.20 mmol) in 2-propanol (3 mL) was added 2 drops of concentrated HCl. The mixture was heated to 180° C. in a microwave for 25 min. The reaction mixture was diluted with 20 mL DCM and 5 mL MeOH, and washed with saturated aqueous NaHCO3. The aqueous layer was extracted with DCM, and the combined organic layers were dried over Na2SO4, filtered, and purified by flash chromatography to give the title compound (24 mg, 24% yield). 1H NMR (400 MHz, d6-DMSO): δ 10.94 (s, 1H), 9.52 (s, 1H), 8.85 (d, J=7.0 Hz, 1H), 8.51 (d, J=9.2 Hz, 1H), 8.27 (d, J=5.1 Hz, 1H), 8.02 (s, 1H), 7.83 (d, J=7.8 Hz, 1H), 7.74 (s, 1H), 7.46-7.60 (m, 4H), 7.36 (d, J=7.9 Hz, 1H), 7.26 (t, J=8.1 Hz, 2H), 7.12-7.21 (m, 2H), 6.92 (d, J=7.7 Hz, 1H), 6.53 (d, J=5.2 Hz, 1H), 3.66 (s, 2H), 2.54-2.57 (m, 2H), 2.27-2.33 (m, 2H), 2.08 (s, 6H). MS (ESI) m/z=620 [M+H]+.

Workup

  1. customprepared
  2. washwashed with saturated aqueous NaHCO3
  3. extractionThe aqueous layer was extracted with DCM
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. custompurified by flash chromatography

Sources & evidence

ORD record
ord-dac58c4416b84853a682e60bd77d06e1
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

Loading…