Diisopropylethylamine → Thiazole-2-carboxylic acid {3-[(1-methyl-1H-pyrazole-3-carbonyl)-amino]-adamantan-1-yl}-amide

HRID 218029

반응식

HRID 218029 반응식
[C:1]12([NH2:12])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][C:3]([NH2:11])([CH2:4]3)[CH2:2]1)[CH2:8]2.CCN(C(C)C)C(C)C.[CH3:22][N:23]1[CH:27]=[CH:26][C:25]([C:28](Cl)=[O:29])=[N:24]1.[S:31]1[CH:35]=[CH:34][N:33]=[C:32]1[C:36](Cl)=[O:37]>C(Cl)Cl>[CH3:22][N:23]1[CH:27]=[CH:26][C:25]([C:28]([NH:12][C:1]23[CH2:10][CH:5]4[CH2:6][CH:7]([CH2:9][C:3]([NH:11][C:36]([C:32]5[S:31][CH:35]=[CH:34][N:33]=5)=[O:37])([CH2:4]4)[CH2:2]2)[CH2:8]3)=[O:29])=[N:24]1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 213512Adamantane-1,3-diamineHCID 27952111,3-Thiazole-2-carbonyl chlorideHCID 128450451-Methyl-1H-pyrazole-3-carbonyl chloride

생성물 1

HCID 44633204Thiazole-2-carboxylic acid {3-[(1-methyl-1H-pyrazole-3-carbonyl)-amino]-adamantan-1-yl}-amide수율 38.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of adamantane-1,3-diamine (17 mg, 0.1 mmol, Zerenex Molecular Ltd., Greater Manchester, UK) in DCM (2 mL) was added DIEA (20 mg, 0.15 mmol), 1-methyl-1H-pyrazole-3-carbonyl chloride (16 mg, 0.11 mmol; Maybridge Chemical Co., Cornwall, UK) and thiazole-2-carbonyl chloride (16 mg, 0.11 mmol; Maybridge Chemical Co., Cornwall, UK). After stirring at room temperature for 3 h, the reaction mixture was partitioned into dichloromethane and saturated sodium bicarbonate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified on a RP-HPLC/MS purification system (Gradient: acetonitrile in water, 25-95%, in 3.9 minutes with a cycle time of 5 min. A shallow gradient between 27-53% of acetonitrile was used between 0.75-3.3 min to separate close-eluting impurities. Flow rate: 100 mL/min. Mobile phase additive: 25 mM of ammonium formate. Column: Inertsil® C8, 30×50 mm, 5 μm particle size (GL Sciences, Tokyo, Japan)) to afford 15 mg (38%) of the title compound, thiazole-2-carboxylic acid {3-[(1-methyl-1H-pyrazole-3-carbonyl)-amino]-adamantan-1-yl}-amide, as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J=3.2 Hz, 1H), 7.53 (d, J=3.2 Hz, 1H), 7.33 (d, J=2.3 Hz, 1H), 7.14 (d, J=2.3 Hz, 1H), 6.74-6.71 (m, 2H), 3.89 (s, 3H), 2.55-2.51 (m, 2H), 2.35-2.29 (m, 2H), 2.19-2.11 (m, 8H), 1.71-1.67 (m, 2H), ESI-MS m/z: 386.0 (M+H)+.

후처리

  1. customthe reaction mixture was partitioned into dichloromethane and saturated sodium bicarbonate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified on a RP-HPLC/MS purification system (Gradient
  5. waitacetonitrile in water, 25-95%, in 3.9 minutes with a cycle time of 5 min
  6. waitA shallow gradient between 27-53% of acetonitrile was used between 0.75-3.3 min
  7. customto separate
  8. washclose-eluting impurities

출처 및 근거

ORD 기록
ord-916d88438a0c4c5882ee8ee9d2dd35dc
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08198275B2

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