Methylamine → 3-(2-(5-bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)-N-methylpropanamide

HRID 335192

Reaction equation

HRID 335192 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([O:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH2:14][CH2:15][C:16]([OH:18])=O)[N:13]=2)=[N:6][CH:7]=1.C1C=CC2N(O)N=[N:32][C:30]=2C=1.O.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.CN>C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]([O:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH2:14][CH2:15][C:16]([NH:32][CH3:30])=[O:18])[N:13]=2)=[N:6][CH:7]=1

Participants

7

Reactant 5

HCID 6329MethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 577426713-(2-(5-Bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)propanoic acid

Product 1

HCID 577428013-(2-(5-bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)-N-methylpropanamideYield 69.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-(2-(5-bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)propanoic acid (0.100 g, 0.238 mmol) (Example 315) HOBT-H2O (0.0547 g, 0.357 mmol), DIEA (d 0.742) (0.0870 mL, 0.500 mmol), EDCI (0.0684 g, 0.357 mmol), and methanamine (0.238 mL, 0.476 mmol) in 10 mL acetonitrile was stirred at ambient temperature for 5 hours and then heated at 50° C. overnight. The mixture was concentrated to a residue, dissolved in THF and precipitated with the addition of water. The solids were filtered, washed with water and dried on high vacuum overnight to give the title compound (0.072 g, 69.8% yield) as white solids. 1H NMR (d6 DMSO) δ 2.41 (t, J=7.8 Hz, 2H), 2.56 (d, J=4.7 Hz, 3H), 2.79 (t, J=7.7 Hz, 2H), 6.62 (s, 1H), 7.10 (d, J=8.0 Hz, 2H), 7.21 (t, J=7.3 Hz, 1H), 7.40 (d, J=2.0 Hz, 1H), 7.43 (t, J=7.9 Hz, 2H), 7.77 (d, J=4.3 Hz, 1H), 8.21 (d, J=2.0 Hz, 1H), 10.94 (br s, 1H).

Workup

  1. temperatureheated at 50° C. overnight
  2. concentrationThe mixture was concentrated to a residue
  3. dissolutiondissolved in THF
  4. customprecipitated with the addition of water
  5. filtrationThe solids were filtered
  6. washwashed with water
  7. customdried on high vacuum overnight

Sources & evidence

ORD record
ord-b28e279c350f4e64adc71910d5b4c7b4
Source dataset
uspto-grants-2014_11
Patent number
US08883828B2

Linked notes

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