Pyridine → HCID 86274674, compound

HRID 626577Notes

Reaction equation

HRID 626577 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[C:3]([NH2:5])=[O:4].C(Cl)(=O)[C:9](Cl)=[O:10].[NH2:14][C:15]1[N:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]([N:31]3[CH2:35][CH2:34][C@@H:33]([N:36]([CH3:38])[CH3:37])[CH2:32]3)=[O:30])[CH:23]=2)=[CH:17][CH:16]=1.N1C=CC=CC=1>ClCCCl.C1COCC1>[CH3:37][N:36]([CH3:38])[C@@H:33]1[CH2:34][CH2:35][N:31]([C:29]([NH:28][C:24]2[CH:23]=[C:22]([O:21][C:18]3[CH:19]=[N:20][C:15]([NH:14][C:9]([NH:5][C:3](=[O:4])[C:2]([CH3:7])([CH3:6])[CH3:1])=[O:10])=[CH:16][CH:17]=3)[CH:27]=[CH:26][N:25]=2)=[O:30])[CH2:32]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 90411101HCID 90411101, compound

Product 1

HCID 86274674HCID 86274674, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2,2,2-trimethylacetamide (0.248 g, 2.453 mmol) in DCE (5 mL) was treated with oxalyl chloride (0.197 mL, 2.331 mmol), heated at 100° C. for 1 h, cooled to RT, added drop-wise to a solution of (R)—N-(4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)-3-(dimethylamino)pyrrolidine-1-carboxamide (0.600 g, 1.752 mmol) and pyridine (0.198 mL, 2.453 mmol) in THF (10 mL) and stirred at RT overnight. The mixture was concentrated to dryness, treated with satd. NH4Cl, extracted with EtOAc (4×) and the combined organics were washed with water, dried over Na2SO4 and concentrated to dryness. The residue was suspended in MeCN, sonicated and the resulting solid collected via filtration to afford (R)-3-(dimethylamino)-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)pyrrolidine-1-carboxamide (280 mg, 34%). 1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1H), 10.44 (br s, 1H), 8.78 (s, 1H), 8.23 (d, J=2.9 Hz, 1H), 8.11 (d, J=5.7 Hz, 1H), 8.08 (d, J=8.9 Hz, 1H), 7.71 (dd, J=9.0, 2.9 Hz, 1H), 7.46 (d, J=2.4 Hz, 1H), 6.61 (dd, J=5.7, 2.4 Hz, 1H), 3.62 (m, 1H), 3.52 (m, 1H), 3.27 (m, 1H), 3.08 (m, 1H), 2.65 (m, 1H), 2.15 (s, 6H), 2.08-1.95 (m, 1H), 1.65 (m, 1H), 1.21 (s, 9H); MS (ESI) m/z: 470.3 (M+H+).

Workup

  1. temperaturecooled to RT
  2. concentrationThe mixture was concentrated to dryness
  3. additiontreated with satd
  4. extractionNH4Cl, extracted with EtOAc (4×)
  5. washthe combined organics were washed with water
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. customsonicated
  9. filtrationthe resulting solid collected via filtration

Sources & evidence

ORD record
ord-12fb930894d14ed29c40f018b85f4d72
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

Loading…