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Hydrochloric Acid → N-(2,6-difluorophenyl)-3-{3-[2-({2-(ethyloxy)-4-[4-(1-methylethyl)-1-piperazinyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamide

HRID 419543
Notes
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Reaction equation

HRID 419543 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.[CH2:34]([O:36][C:37]1[CH:42]=[C:41]([N:43]2[CH2:48][CH2:47][N:46]([CH:49]([CH3:51])[CH3:50])[CH2:45][CH2:44]2)[CH:40]=[CH:39][C:38]=1[NH2:52])[CH3:35].Cl.O1CCOCC1.C[O-].[Na+]>FC(F)(F)CO.CO.C(Cl)Cl.CCCCCC>[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:52][C:38]3[CH:39]=[CH:40][C:41]([N:43]4[CH2:48][CH2:47][N:46]([CH:49]([CH3:50])[CH3:51])[CH2:45][CH2:44]4)=[CH:42][C:37]=3[O:36][CH2:34][CH3:35])[N:7]=2)[CH:18]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 10942334Sodium MethoxideHCID 59452785(2-(Ethyloxy)-4-[4-(1-methylethyl)-1-piperazinyl]phenyl}amineHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

Product 1

HCID 59452822
N-(2,6-difluorophenyl)-3-{3-[2-({2-(ethyloxy)-4-[4-(1-methylethyl)-1-piperazinyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamide
Yield 66%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 64092,2,2-TrifluoroethanolSolventHCID 8058HexaneSolvent

Conditions

Temperature
175 °C

Procedure

To 3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (100 mg, 0.22 mmol) and {2-(ethyloxy)-4-[4-(1-methylethyl)-1-piperazinyl]phenyl}amine (57 mg, 0.22 mmol) in 2,2,2-trifluoroethanol (1.1 mL) was added 4 M HCl in dioxane (108 μL, 0.43 mmol). The mixture was stirred and heated on a Biotage microwave at 175° C. for 30 min, then cooled to rt. The mixture was neutralized with 0.5M sodium methoxide in MeOH. The mixture was concentrated under vacuum and the residue purified by silica gel chromatography to give a yellow oil. The oil was dissolved in minimal DCM, then hexane was added until a precipitate was formed. The slurry was cooled at −10° C. for 30 min, then poured through a Teflon filter, washing the solids with cold hexanes. The solids were dried under vacuum to give the title compound (98 mg, 0.14 mmol, 66%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 10.24 (s, 1H), 9.38 (brs, 1H), 8.36 (d, 2H, J=14.66 Hz), 8.23 (d, 1H, J=5.13 Hz), 8.05 (d, 1H, J=7.88 Hz), 7.81 (d, 1H, J=7.88 Hz), 7.73 (d, 1H, J=9.16 Hz), 7.61 (t, 1H, J=7.70 Hz), 7.36-7.49 (m, 3H), 7.21 (t, 2H, J=8.06 Hz), 6.97 (t, 1H, J=6.87 Hz), 6.65 (s, 1H), 6.45-6.50 (m, 2H), 4.06 (q, 2H, J=7.03 Hz), 3.08-3.14 (m, 4H), 2.64-2.69 (m, 1H), 2.54-2.61 (m, 4H), 1.24 (t, 3H, J=6.96 Hz), 1.00 (d, 6H, J=6.23 Hz). MS (ESI): 689 [M+H]+.

Workup

  1. temperaturecooled to rt
  2. concentrationThe mixture was concentrated under vacuum
  3. customthe residue purified by silica gel chromatography
  4. customto give a yellow oil
  5. customwas formed
  6. temperatureThe slurry was cooled at −10° C. for 30 min
  7. filtrationfilter
  8. washwashing the solids with cold hexanes
  9. customThe solids were dried under vacuum

Sources & evidence

ORD record
ord-334991e72e1e4c3e81c2a3533ff9706e
Source dataset
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08093239B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes