HCID 28972681, compound → HCID 57737188, compound

HRID 1157537Notes

Reaction equation

HRID 1157537 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:31])[CH2:25][C:26]4[S:27][CH:28]=[CH:29][CH:30]=4)[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.[CH3:32][N:33]([CH3:46])[CH2:34][CH2:35][CH2:36][NH:37][C:38]1[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][C:39]=1[F:45]>CC(O)C.Cl>[CH3:46][N:33]([CH3:32])[CH2:34][CH2:35][CH2:36][NH:37][C:38]1[CH:43]=[CH:42][C:41]([NH:44][C:2]2[N:7]=[C:6]([C:8]3[C:9]([C:17]4[CH:18]=[C:19]([NH:23][C:24](=[O:31])[CH2:25][C:26]5[S:27][CH:28]=[CH:29][CH:30]=5)[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][C:39]=1[F:45]

Participants

5

Reactant 2

HCID 28972681HCID 28972681, compound2×HCID 57737219HCID 57737219, compound

Product 1

HCID 57737188HCID 57737188, compoundYield 36.6%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
120 °C

Procedure

To a slurry of N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide (100 mg, 0.22 mmol.) in i-PrOH (4 mL) was added N1-[3-(dimethylamino)propyl]-2-fluoro-1,4-benzenediamine (75 mg, 0.30 mmol) and 2 drops of conc. HCl. The reaction was heated in a microwave to 120° C. for 20 min. and allowed to cool to rt. A second batch of N1-[3-(dimethylamino)propyl]-2-fluoro-1,4-benzenediamine (75 mg, 0.30 mmol) was added and the reaction microwaved to 120° C. for 1 h further. The reaction was concentrated and the crude purified by HPLC (Agilent, 50-90% gradient over 15 min.) to give the title compound (50 mg, 36% yield) as an oil which solidified to a dark green solid. 1H NMR (400 MHz, d6-DMSO) δ 10.33 (s, 1H), 9.27 (s, 1H), 8.79 (d, J=7.0 Hz, 1H), 8.42 (bd, J=6.8 Hz, 1H), 8.15-8.17 (m, 2H), 7.85 (s, 1H), 7.71 (d, J=8.4 Hz, 1H), 7.51 (d, J=14.3 Hz, 1H), 7.35-7.43 (m, 3H), 7.23 (d, J=7.5 Hz, 1H), 7.18 (d, J=8.6 Hz, 1H), 7.08 (t, J=7.8 Hz, 1H), 6.93-6.95 (m, 2H), 6.60 (t, J=9.4 Hz, 1H), 6.38 (d, J=5.3 Hz, 1H), 3.84 (s, 2H), 3.05 (t, J=7.0 Hz, 2H), 2.37 (t, J=7.0 Hz, 2H), 2.18 (s, 6H), 1.69 (quintet, J=7.0 Hz, 2H) ppm. ES-LC/MS m/z=621 [M+H]+.

Workup

  1. temperatureto cool to rt
  2. customthe reaction microwaved to 120° C. for 1 h further
  3. concentrationThe reaction was concentrated
  4. customthe crude purified by HPLC (Agilent, 50-90% gradient over 15 min.)

Sources & evidence

ORD record
ord-fb85c371b25d49fbb8dedaf2fa2dfea6
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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