Water → HCID 86270218, compound

HRID 2278983Notes

Reaction equation

HRID 2278983 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[C:11]([O:13][C:14]3[CH:15]=[CH:16][C:17]([NH2:20])=[N:18][CH:19]=3)[CH:10]=[CH:9][N:8]=2)[CH:4]=[N:3]1.N1C=CC=CC=1.[CH3:27][O:28][CH2:29][CH2:30][CH2:31][N:32]1[CH2:36][CH2:35][N:34]([C:37](Cl)=[O:38])[C:33]1=[O:40].O>C(Cl)Cl.C1COCC1>[CH3:27][O:28][CH2:29][CH2:30][CH2:31][N:32]1[CH2:36][CH2:35][N:34]([C:37]([NH:20][C:17]2[CH:16]=[CH:15][C:14]([O:13][C:11]3[CH:10]=[CH:9][N:8]=[C:7]([C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)[CH:12]=3)=[CH:19][N:18]=2)=[O:38])[C:33]1=[O:40]

Participants

7

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 593227775-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amineHCID 90426395HCID 90426395, compound

Product 1

HCID 86270218HCID 86270218, compoundYield 57.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A 0° C. mixture of Example A2 (0.160 g, 0.599 mmol) and pyridine (0.15 mL, 1.862 mmol) in DCM (5 mL) was treated with a solution of 3-(3-methoxypropyl)-2-oxoimidazolidine-1-carbonyl chloride (0.264 g, 1.197 mmol) in THF (5 mL), warmed to RT and stirred overnight. The mixture was treated with water, stirred for 10 min, the layers separated and the aqueous layer extracted with DCM (2×). The combined organics were dried over Na2SO4, concentrated to dryness, purified via silica gel chromatography (MeOH/DCM) and the resulting material was treated with Et2O and the solid collected via filtration to afford 3-(3-methoxypropyl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide (155 mg, 57%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.97 (s, 1 H), 8.36 (d, J=5.7 Hz, 1 H), 8.25 (s, 1 H), 8.22 (d, J=2.9 Hz, 1 H), 8.07 (d, J=9.0 Hz, 1 H), 7.96 (s, 1 H), 7.72 (dd, J=9.0, 2.9 Hz, 1 H), 7.22 (d, J=2.4 Hz, 1 H), 6.69 (dd, J=5.7, 2.4 Hz, 1 H), 3.84 (s, 3 H), 3.81-3.79 (m, 2 H), 3.46 (m, 2 H), 3.34 (m, 2 H), 3.27 (m, 2 H), 3.22 (s, 3 H), 1.77-1.69 (m, 2 H); MS (ESI) m/z: 452.2 (M+H+).

Workup

  1. stirringstirred for 10 min
  2. customthe layers separated
  3. extractionthe aqueous layer extracted with DCM (2×)
  4. dry with materialThe combined organics were dried over Na2SO4
  5. concentrationconcentrated to dryness
  6. custompurified via silica gel chromatography (MeOH/DCM)
  7. additionthe resulting material was treated with Et2O
  8. filtrationthe solid collected via filtration

Sources & evidence

ORD record
ord-e7a6f986f85f445bb8c211810ce6cacf
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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