Hydrochloric Acid → N-(2,6-difluorophenyl)-2-(ethyloxy)-5-(3-{2-[(2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamide

HRID 419586Notes

Reaction equation

HRID 419586 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]([CH2:52][CH2:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH2:48][CH2:47]2)[CH:43]=[CH:42][C:40]=1[NH2:41].Cl>FC(F)(F)CO>[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]([CH2:52][CH2:53][S:54]([CH3:57])(=[O:56])=[O:55])[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 313Hydrochloric AcidHCID 594529415-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamideHCID 666497682-(Methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}aniline

Product 1

HCID 59860248N-(2,6-difluorophenyl)-2-(ethyloxy)-5-(3-{2-[(2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamideYield 44%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Conditions

Temperature
180 °C

Procedure

To 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide (Intermediate Example 6) (0.13 g, 0.25 mmol) and 2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}aniline (0.077 g, 0.25 mmol) in 2,2,2-trifluoroethanol (1.5 mL) was added HCl (0.13 mL, 4M in dioxane, 0.50 mmol). The reaction was heated at 180° C. for 40 min in the microwave. The reaction mixture was quenched with sodium methoxide (0.5M in MeOH) and concentrated. Purification by flash chromatography, and recrystallization with EtOH provided the title compound (0.082 g, 0.11 mmol, 43%). 1H NMR (400 MHz, DMSO-d6) δ 1.19-1.30 (m, 2H), 1.39 (t, J=6.6 Hz, 3H), 1.43-1.53 (m, 1H), 1.57-1.68 (m, 2H), 1.74 (d, J=13.9 Hz, 2H), 2.53-2.64 (m, 2H), 2.92 (s, 3H), 3.07-3.18 (m, 2H), 3.66 (d, J=11.4 Hz, 2H), 3.76 (s, 3H), 4.23 (d, J=6.2 Hz, 2H), 6.43-6.53 (m, 2H), 6.63 (s, 1H), 6.86-6.97 (m, 1H), 7.15 (t, J=7.6 Hz, 2H), 7.23 (d, J=8.4 Hz, 1H), 7.32-7.43 (m, 3H), 7.66 (d, J=9.2 Hz, 1H), 7.71 (d, J=11.5 Hz, 1H), 8.01 (s, 1H), 8.16 (d, J=5.5 Hz, 1H), 8.39 (s, 1H), 9.33 (br. s., 1H), 9.71 (s, 1H). MS (ESI) m/z=782 [M+H]+.

Workup

  1. customThe reaction mixture was quenched with sodium methoxide (0.5M in MeOH)
  2. concentrationconcentrated
  3. customPurification
  4. customby flash chromatography, and recrystallization with EtOH

Sources & evidence

ORD record
ord-a060ea6fd0bd43dcb7b1d5b8b0db562d
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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