Hydrochloric Acid → N-(2,6-Difluorophenyl)-3-[3-[2-[[2-methoxy-4-[4-(1-piperidinylmethyl)-1-piperidinyl]phenyl]amino]-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl]benzamide

HRID 419348Notes

Reaction equation

HRID 419348 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.[CH3:34][O:35][C:36]1[CH:42]=[C:41]([N:43]2[CH2:48][CH2:47][CH:46]([CH2:49][N:50]3[CH2:55][CH2:54][CH2:53][CH2:52][CH2:51]3)[CH2:45][CH2:44]2)[CH:40]=[CH:39][C:37]=1[NH2:38].Cl>C(O)C(F)(F)F>[F:30][C:24]1[CH:25]=[CH:26][CH:27]=[C:28]([F:29])[C:23]=1[NH:22][C:20](=[O:21])[C:19]1[CH:31]=[CH:32][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:38][C:37]3[CH:39]=[CH:40][C:41]([N:43]4[CH2:48][CH2:47][CH:46]([CH2:49][N:50]5[CH2:55][CH2:54][CH2:53][CH2:52][CH2:51]5)[CH2:45][CH2:44]4)=[CH:42][C:36]=3[O:35][CH3:34])[N:7]=2)[CH:18]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 59452773HCID 59452773, compoundHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

Product 1

HCID 59452800N-(2,6-Difluorophenyl)-3-[3-[2-[[2-methoxy-4-[4-(1-piperidinylmethyl)-1-piperidinyl]phenyl]amino]-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl]benzamideYield 46%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

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) (0.11 g, 0.25 mmol) and 2-(methyloxy)-4-[4-(1-piperidinylmethyl)-1-piperidinyl]aniline (0.076 g, 0.25 mmol) in trifluoroethanol (1.5 mL) was added HCl (0.13 mL, 4M in dioxane, 0.50 mmol). The reaction was heated at 170° C. for 80 min in the microwave. When complete by MS, the reaction mixture was quenched with sodium methoxide (0.5M in MeOH) and concentrated. Purification by flash chromatography, followed by prep-HPLC, and recrystallization with DCM/hexanes provided the title compound (0.082 g, 0.11 mmol, 46%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.14-1.26 (m, 2H), 1.36 (br. s., 2H), 1.43-1.53 (m, 4H), 1.63 (br. s., 1H), 1.77 (d, J=11.7 Hz, 2H), 2.09 (d, J=7.0 Hz, 2H), 2.27 (s, 4H), 2.63 (t, J=12.1 Hz, 2H), 3.67 (d, J=11.4 Hz, 2H), 3.78 (s, 3H), 6.40-6.51 (m, 2H), 6.65 (d, J=2.2 Hz, 1H), 6.97 (t, J=7.0 Hz, 1H), 7.20 (t, J=8.1 Hz, 2H), 7.35-7.42 (m, 2H), 7.44-7.48 (m, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.72 (d, J=9.2 Hz, 1H), 7.81 (d, J=7.7 Hz, 1H), 8.05 (d, J=8.1 Hz, 1H), 8.19 (d, J=5.1 Hz, 1H), 8.33 (s, 1H), 8.46 (s, 1H), 9.40 (br. s., 1H), 10.24 (s, 1H). MS (M+H, ES+) 729.

Workup

  1. customWhen complete by MS, the reaction mixture was quenched with sodium methoxide (0.5M in MeOH)
  2. concentrationconcentrated
  3. customPurification by flash chromatography
  4. customrecrystallization with DCM/hexanes

Sources & evidence

ORD record
ord-275e401b94af47b4bd117a8fea34b864
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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