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

HRID 1806118노트

반응식

HRID 1806118 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-77beb0fe8ee7436b9058c8f3c613cd15
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08354540B2

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