4-(1,4'-Bipiperidin-1'-yl)-2-[(2-methylpropyl)oxy]aniline → 3-{3-[2-({4-(1,4'-bipiperidin-1'-yl)-2-[(2-methylpropyl)oxy]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}-N-(2,6-difluorophenyl)benzamide

HRID 419343Notes

Reaction equation

HRID 419343 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]=[C:19]([CH:31]=[CH:32][CH:33]=2)[C:20]([NH:22][C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=2[F:30])=[O:21])[CH:5]=[CH:4][N:3]=1.[N:34]1([CH:40]2[CH2:45][CH2:44][N:43]([C:46]3[CH:52]=[CH:51][C:49]([NH2:50])=[C:48]([O:53][CH2:54][CH:55]([CH3:57])[CH3:56])[CH:47]=3)[CH2:42][CH2:41]2)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>CC(O)C.Cl>[N:34]1([CH:40]2[CH2:45][CH2:44][N:43]([C:46]3[CH:52]=[CH:51][C:49]([NH:50][C:2]4[N:7]=[C:6]([C:8]5[N:12]6[CH:13]=[CH:14][CH:15]=[CH:16][C:11]6=[N:10][C:9]=5[C:17]5[CH:18]=[C:19]([CH:31]=[CH:32][CH:33]=5)[C:20]([NH:22][C:23]5[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=5[F:30])=[O:21])[CH:5]=[CH:4][N:3]=4)=[C:48]([O:53][CH2:54][CH:55]([CH3:57])[CH3:56])[CH:47]=3)[CH2:42][CH2:41]2)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1

Participants

5

Reactant 2

HCID 594527114-(1,4'-Bipiperidin-1'-yl)-2-[(2-methylpropyl)oxy]anilineHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

Product 1

HCID 594529923-{3-[2-({4-(1,4'-bipiperidin-1'-yl)-2-[(2-methylpropyl)oxy]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}-N-(2,6-difluorophenyl)benzamideYield 37.5%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
170 °C

Procedure

To 3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (0.12 g, 0.25 mmol) and 4-(1,4′-bipiperidin-1′-yl)-2-[(2-methylpropyl)oxy]aniline (0.081 g, 0.24 mmol) in anhydrous iPrOH (3 mL) was added HCl (2 drops, 37% weight in H2O). The reaction was heated at 170° C. for 33 min in the microwave. The reaction mixture was poured into half saturated NaCO3, extracted with DCM and EtOAc, dried (MgSO4) and concentrated. Purification by flash chromatography followed by prep-HPLC provided the title compound (0.07 g, 0.09 mmol, 36%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.78 (d, J=6.6 Hz, 6H), 1.33-1.42 (m, 2H), 1.47 (s, 3H), 1.54 (d, J=11.7 Hz, 3H), 1.72-1.82 (m, 2H), 1.82-1.93 (m, 2H), 2.31 (s, 2H), 2.45 (s, 3H), 2.58-2.69 (m, 2H), 3.75 (d, J=6.2 Hz, 3H), 6.41-6.50 (m, 2H), 6.66 (s, 1H), 6.87-6.98 (m, 1H), 7.20 (t, J=8.2 Hz, 2H), 7.29 (d, J=10.6 Hz, 1H), 7.35-7.47 (m, 2H), 7.59 (t, J=7.9 Hz, 1H), 7.71 (d, J=9.2 Hz, 1H), 7.79 (d, J=7.7 Hz, 1H), 8.04 (d, J=8.1 Hz, 1H), 8.20 (d, J=5.1 Hz, 1H), 8.32 (s, 1H), 8.43 (s, 1H), 9.31 (d, J=9.9 Hz, 1H), 10.23 (s, 1H). MS (M+H, ES+) 757.

Workup

  1. extractionextracted with DCM and EtOAc
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customPurification by flash chromatography

Sources & evidence

ORD record
ord-2ca35e726b6543e69fe1c09cc881bb8c
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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