p-Toluenesulfonic acid → HCID 59452792, compound

HRID 419642Notes

Reaction equation

HRID 419642 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]3=[N:10][C:9]=2[C:17]2[CH:18]=[CH:19][C:20]([O:34][CH2:35][CH3:36])=[C:21]([CH:33]=2)[C:22]([NH:24][C:25]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=2[F:32])=[O:23])[CH:5]=[CH:4][N:3]=1.[CH3:37][O:38][C:39]1[CH:45]=[C:44]([N:46]2[CH2:51][CH2:50][CH:49]([N:52]3[CH2:57][CH2:56][N:55]([S:58]([CH3:61])(=[O:60])=[O:59])[CH2:54][CH2:53]3)[CH2:48][CH2:47]2)[CH:43]=[CH:42][C:40]=1[NH2:41].C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(O)C>[F:32][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]([F:31])[C:25]=1[NH:24][C:22](=[O:23])[C:21]1[CH:33]=[C:17]([C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]3[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:41][C:40]3[CH:42]=[CH:43][C:44]([N:46]4[CH2:51][CH2:50][CH:49]([N:52]5[CH2:57][CH2:56][N:55]([S:58]([CH3:61])(=[O:60])=[O:59])[CH2:54][CH2:53]5)[CH2:48][CH2:47]4)=[CH:45][C:39]=3[O:38][CH3:37])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH2:35][CH3:36]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 574161512-(Methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}anilineHCID 594529415-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide

Product 1

HCID 59452792HCID 59452792, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
175 °C

Procedure

A mixture of 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide (Intermediate Example 6) (0.10 g, 0.20 mmol), 2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}aniline (Example 58, Step B) (0.073 g, 0.20 mmol) and para-toluenesulfonic acid (0.090 g, 0.47 mmol) in i-PrOH (5 mL) was heated in a microwave at 175° C. for 25 min. The reaction mixture was concentrated onto silica gel and purified by flash chromatography. Recrystallization from DCM and diethyl ether afforded N-(2,6-difluorophenyl)-2-(ethyloxy)-5-(3-{2-[(2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}-imidazo[1,2-a]pyridin-2-yl)benzamide (0.066 g, 40%) as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.76 (s, 1H), 9.37 (br. s., 1H), 8.45 (s, 1H), 8.21 (d, J=5.2 Hz, 1H), 8.06 (d, J=1.5 Hz, 1H), 7.65-7.81 (m, 2H), 7.35-7.50 (m, 3H), 7.28 (d, J=8.6 Hz, 1H), 7.16-7.25 (m, 2H), 6.88-7.02 (m, 1H), 6.69 (d, J=2.3 Hz, 1H), 6.46-6.61 (m, 2H), 4.22-4.33 (m, 2H), 3.81 (s, 3H), 3.71-3.79 (m, 2H), 3.03-3.15 (m, 4H), 2.87 (s, 3H), 2.64-2.73 (m, 2H), 2.58-2.64 (m, 4H), 2.38-2.46 (m, 1H), 1.80-1.89 (m, 2H), 1.50-1.62 (m, 2H), 1.44 (t, J=6.9 Hz, 3H). MS (M+H, ES+) 838.

Workup

  1. concentrationThe reaction mixture was concentrated onto silica gel
  2. custompurified by flash chromatography
  3. customRecrystallization from DCM and diethyl ether

Sources & evidence

ORD record
ord-ac0641bdc63349b89177f10d6fe367ae
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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