1,2-Dichloroethane → HCID 86267640, compound

HRID 1049325Notes

Reaction equation

HRID 1049325 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([NH:8][C:9]([NH:11][C:12]([CH:14]2[CH2:18]CO[CH2:15]2)=[O:13])=[O:10])[CH:5]=[CH:4][C:3]=1[O:19][C:20]1[CH:25]=[CH:24][N:23]=[C:22]([C:26]2[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=2)[CH:21]=1.[C:32](Cl)(=O)C(Cl)=O.N1C=CC=CC=1.Cl[CH2:45][CH2:46]Cl>C1COCC1>[CH3:32][C:45]1([CH3:46])[CH2:15][CH:14]([C:12]([NH:11][C:9](=[O:10])[NH:8][C:6]2[CH:5]=[CH:4][C:3]([O:19][C:20]3[CH:25]=[CH:24][N:23]=[C:22]([C:26]4[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=4)[CH:21]=3)=[C:2]([CH3:1])[N:7]=2)=[O:13])[CH2:18]1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 1049PyridineHCID 65578Oxalyl chlorideHCID 86270460HCID 86270460, compound

Product 1

HCID 86267640HCID 86267640, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
83 °C

Procedure

A suspension of Example B (0.054 g, 0.427 mmol) in DCE (4 mL) was treated with oxalyl chloride (0.037 mL, 0.427 mmol), heated at 83° C. for 2 h, cooled to RT and added drop-wise to a solution of Example A6 (0.1 g, 0.355 mmol) in THF (4 mL) and pyridine (0.144 mL, 1.777 mmol). The mixture was stirred at RT for 2 h, treated with satd. NaHCO3, extracted with EtOAc (3×) and the combined organics were dried over MgSO4, concentrated to dryness, triturated with MeCN, and the solid collected via filtration and dried to afford 3,3-dimethyl-N-((6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)cyclobutanecarboxamide (134 mg, 87%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.06 (s, 1H), 10.69 (s, 1H), 8.35 (d, J=5.7 Hz, 1H), 8.25 (s, 1H), 7.95 (s, 1H), 7.90 (d, J=8.8 Hz, 1H), 7.61 (d, J=8.8 Hz, 1H), 7.16 (d, J=2.4 Hz, 1H), 6.60 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 3.24 (m, 1H), 2.26 (s, 3H), 2.02-1.87 (m, 4H), 1.13 (s, 3H), 1.05 (s, 3H); MS (ESI) m/z: 435.2 (M+H+).

Workup

  1. temperaturecooled to RT
  2. additiontreated with satd
  3. extractionNaHCO3, extracted with EtOAc (3×)
  4. dry with materialthe combined organics were dried over MgSO4
  5. concentrationconcentrated to dryness
  6. customtriturated with MeCN
  7. filtrationthe solid collected via filtration
  8. customdried

Sources & evidence

ORD record
ord-cf9da3d31d374ad7938cb65726a2e5b0
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

Loading…