Hydrochloric Acid → HCID 87090176, compound

HRID 419382Notes

Reaction equation

HRID 419382 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.[F:34][CH2:35][CH2:36][N:37]1[CH2:42][C@@H:41]2[CH2:43][C@H:38]1[CH2:39][N:40]2[CH:44]1[CH2:49][CH2:48][N:47]([C:50]2[CH:56]=[CH:55][C:53]([NH2:54])=[C:52]([O:57][CH3:58])[CH:51]=2)[CH2:46][CH2:45]1.Cl.C[O-].[Na+]>C(O)C(F)(F)F.CO.C(Cl)Cl.C(OCC)C>[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:54][C:53]3[CH:55]=[CH:56][C:50]([N:47]4[CH2:48][CH2:49][CH:44]([N:40]5[CH2:39][C@@H:38]6[CH2:43][C@H:41]5[CH2:42][N:37]6[CH2:36][CH2:35][F:34])[CH2:45][CH2:46]4)=[CH:51][C:52]=3[O:57][CH3:58])[N:7]=2)[CH:18]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 10942334Sodium MethoxideHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamideHCID 86625192HCID 86625192, compound

Product 1

HCID 87090176HCID 87090176, compoundYield 27%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 64092,2,2-TrifluoroethanolSolvent

Conditions

Temperature
85 °C

Procedure

To 3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (260 mg, 0.57 mmol) and 4-{4-[(1S,4S)-5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-1-piperidinyl}-2-(methyloxy)aniline (200 mg, 0.57 mmol) in trifluoroethanol (2 mL) was added concentrated HCl (0.14 mL, 1.7 mmol). The reaction was heated in a sealed-tube at 85° C. for two days. After cooling to rt 0.5 N sodium methoxide in MeOH (4 mL) was added to the reaction. The solvent was removed under vacuum. DCM and silica gel were added, and the solvent removed under vacuum. The material was purified by flash chromatography. The desired fractions were combined and the solvent removed on the rotovap to give product. The material was dissolved in DCM then diethyl ether was added until the solution just turns cloudy. The solution was placed in the refrigerator. The title compound was obtained as yellow crystals which were collected by vacuum filtration, washing with ether. (120 mg, 0.15 mmol, 27% yield). 1H NMR (400 MHz, DMSO-d6) δ10.16 (s, 1H), 9.31 (brs, 1H), 8.38 (s, 1H), 8.25 (s, 1H), 8.12 (d, J=5.1 Hz, 1H), 7.97 (d, J=7.7 Hz, 1H), 7.73 (d, J=7.5 Hz, 1H), 7.64 (d, J=9.0 Hz, 1H), 7.53 (dd, J=7.9, 7.7 Hz, 1H), 7.42-7.25 (m, 3H), 7.12 (dd, J=8.1, 8.1 Hz, 2H), 6.89 (dd, J=6.6, 6.6 Hz, 1H), 4.34 (dt, J=47.6, 4.9 Hz, 2H), 3.71 (s, 3H), 3.52 (d, J=11.7 Hz, 2H), 3.39 (s, 1H), 3.17 (s, 1H), 2.82-2.54 (m, 6H), 2.51 (d, J=9.3 Hz, 1H), 2.42-2.30 (m under DMSO peak, 2H), 1.78 (d, J=11.9 Hz, 1H), 1.69 (d, J=11.9 Hz, 1H), 1.50 (d, J=8.8 Hz, 1H), 1.42 (d, J=8.8 Hz, 1H), 1.38-1.25 (m, 2H).

Workup

  1. additionwas added to the reaction
  2. customThe solvent was removed under vacuum
  3. additionDCM and silica gel were added
  4. customthe solvent removed under vacuum
  5. customThe material was purified by flash chromatography
  6. customthe solvent removed on the rotovap
  7. customto give product

Sources & evidence

ORD record
ord-e53e7e287a844aae88b29b530b7e7953
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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