Pyridine → HCID 90403467, compound

HRID 1049339Notes

Reaction equation

HRID 1049339 reaction equation
[CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2[CH2:8][C:9]([NH2:11])=[O:10].C(Cl)(=O)[C:13](Cl)=[O:14].[CH3:18][N:19]1[CH:23]=[C:22]([C:24]2[CH:29]=[C:28]([O:30][C:31]3[CH:32]=[CH:33][C:34]([NH2:37])=[N:35][CH:36]=3)[CH:27]=[CH:26][N:25]=2)[CH:21]=[N:20]1.N1C=CC=CC=1>ClCCCl.C1COCC1>[CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2[CH2:8][C:9]([NH:11][C:13](=[O:14])[NH:37][C:34]1[CH:33]=[CH:32][C:31]([O:30][C:28]2[CH:27]=[CH:26][N:25]=[C:24]([C:22]3[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=3)[CH:29]=2)=[CH:36][N:35]=1)=[O:10]

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 1181923676649-95-1HCID 593227775-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amine

Product 1

HCID 90403467HCID 90403467, compoundYield 82.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 2-(bicyclo[2.2.1]heptan-2-yl)acetamide (0.069 g, 0.449 mmol) in DCE (3 mL) was treated with oxalyl chloride (0.039 mL, 0.449 mmol) and heated at 80° C. for 3 h. The mixture was cooled to RT, added drop wise to a solution of Example A2 (0.10 g, 0.374 mmol) and pyridine (0.151 mL, 1.871 mmol) in THF (3 mL) and stirred at RT for 3 days. The mixture was concentrated to dryness and purified via silica gel chromatography (EtOAc, MeOH/DCM). The material was treated with MeCN, the solid collected via filtration and dried to afford 2-(bicyclo[2.2.1]heptan-2-yl)-N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)acetamide (138 mg, 81%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.10 (s, 1H), 10.82 (s, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.26-8.25 (m, 2H), 8.08 (d, J=9.0 Hz, 1H), 7.95 (d, J=0.7 Hz, 1H), 7.72 (dd, J=9.0, 2.9 Hz, 1H), 7.22 (d, J=2.4 Hz, 1H), 6.70 (dd, J=5.7, 2.4 Hz, 1H), 3.83 (s, 3H), 2.36 (dd, J=14.7, 7.8 Hz, 1H), 2.23 (dd, J=14.7, 7.8 Hz, 1H), 2.21 (m, 1H), 1.94 (m, 1H), 1.85 (m, 1H), 1.45-1.38 (m, 3H), 1.31 (m, 1H), 1.11-1.07 (m, 4H); MS (ESI) m/z: 447.3 (M+H+).

Workup

  1. temperatureThe mixture was cooled to RT
  2. concentrationThe mixture was concentrated to dryness
  3. custompurified via silica gel chromatography (EtOAc, MeOH/DCM)
  4. additionThe material was treated with MeCN
  5. filtrationthe solid collected via filtration
  6. customdried

Sources & evidence

ORD record
ord-ef560894053345a7b3bf20918aed2aa1
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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