Water → HCID 86274185, compound

HRID 626561Notes

Reaction equation

HRID 626561 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][C:4](C(O)=O)=[N:3]1.S(Cl)(Cl)=O.[NH2:14][C:15]1[CH:20]=[C:19]([O:21][C:22]2[CH:23]=[CH:24][C:25]([NH:28][C:29]([NH:31][C:32](=[O:37])[C:33]([CH3:36])([CH3:35])[CH3:34])=[O:30])=[N:26][CH:27]=2)[CH:18]=[CH:17][N:16]=1.[OH2:38].N1C=CC=C[CH:40]=1>>[CH3:1][N:2]1[CH:6]=[C:5]([C:40]([NH:14][C:15]2[CH:20]=[C:19]([O:21][C:22]3[CH:27]=[N:26][C:25]([NH:28][C:29]([NH:31][C:32](=[O:37])[C:33]([CH3:34])([CH3:36])[CH3:35])=[O:30])=[CH:24][CH:23]=3)[CH:18]=[CH:17][N:16]=2)=[O:38])[CH:4]=[N:3]1

Participants

6

Reactant 5

HCID 962WaterHCID 1049PyridineHCID 24386Thionyl ChlorideHCID 5731761-methyl-1H-pyrazole-3-carboxylic acidHCID 90409811N-((5-((2-aminopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide

Product 1

HCID 86274185HCID 86274185, compoundYield 64%

Conditions

Temperature
60 °C

Procedure

A suspension of 1-methylpyrazolecarboxylic acid (0.069 g, 0.547 mmol) in thionyl chloride (1.50 mL, 20.66 mmol) was heated at 60° C. for 0.5 h, concentrated to dryness, treated with toluene and concentrated to dryness (3×). The residue was treated with a solution of Example C1 (0.150 g, 0.455 mmol) in pyridine (5 mL) and stirred at RT overnight. The mixture was treated with water, stirred for 0.5 h and the resulting solid collected via filtration. The material was suspended in MTBE, sonicated collected via filtration and purified via silica gel chromatography (MeOH/DCM) to afford 1-methyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)-1H-pyrazole-4-carboxamide (128 mg, 64%). 1H NMR (400 MHz, DMSO-d6): δ 11.23 (s, 1H), 10.58 (s, 1H), 10.44 (s, 1H), 8.39 (s, 1H), 8.27 (d, J=2.9 Hz, 1H), 8.24 (d, J=5.7 Hz, 1H), 8.11-8.09 (m, 1H), 8.08 (d, J=0.7 Hz, 1H), 7.76-7.75 (m, 2H), 6.74 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 1.21 (s, 9H); MS (ESI) m/z: 438.2 (M+H+).

Workup

  1. concentrationconcentrated to dryness
  2. additiontreated with toluene
  3. concentrationconcentrated to dryness (3×)
  4. stirringstirred for 0.5 h
  5. filtrationthe resulting solid collected via filtration
  6. customsonicated
  7. filtrationcollected via filtration
  8. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-2aa01874a97b4760a54bbda6cb86d535
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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