Diisopropylethylamine → 5-Methyl-pyrazine-2-carboxylic acid {3-[(1-methyl-1H-pyrazole-3-carbonyl)-amino]-adamantan-1-yl}-amide

HRID 1020231

反応式

HRID 1020231 の反応式
[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]([OH:30])=O)=[N:24]1.[CH3:31][C:32]1[N:33]=[CH:34][C:35]([C:38](O)=[O:39])=[N:36][CH:37]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>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:38]([C:35]5[CH:34]=[N:33][C:32]([CH3:31])=[CH:37][N:36]=5)=[O:39])([CH2:4]4)[CH2:2]2)[CH2:8]3)=[O:30])=[N:24]1

参加物

7

反応物 5

HCID 81531DiisopropylethylamineHCID 1228315-Methyl-2-pyrazinecarboxylic acidHCID 213512Adamantane-1,3-diamineHCID 5731761-methyl-1H-pyrazole-3-carboxylic acidHCID 2724699PyBOP

生成物 1

HCID 446332035-Methyl-pyrazine-2-carboxylic acid {3-[(1-methyl-1H-pyrazole-3-carbonyl)-amino]-adamantan-1-yl}-amide収率 38%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of adamantane-1,3-diamine (20 mg, 0.1 mmol; Zerenex Molecular Ltd., Greater Manchester, UK) in DCM (2 mL) was added DIEA (26 mg, 0.15 mmol), 1-methyl-1H-pyrazole-3-carboxylic acid (14 mg, 0.11 mmol), 5-methyl-pyrazine-2-carboxylic acid (15 mg, 0.11 mmol) and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (110 mg, 0.20 mmol). After stirring for 3 hours at rt, the reaction mixture was partitioned into dichloromethane and saturated sodium bicarbonate. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified on a RP-HPLC/MS purification system (Gradient: acetonitrile in water, 25-95%, in 3.4 minutes with a cycle time of 5 min. A shallow gradient between 25-50% 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 (37%) of the title compound, 5-methyl-pyrazine-2-carboxylic acid {3-[(1-methyl-1H-pyrazole-3-carbonyl)-amino]-adamantan-1-yl}-amide, as a colorless oil. 1H NMR (400 MHz, CDCl3) δ9.22 (s, 1H), 8.34-8.33 (m, 1H), 7.67 (s, br, 1H), 7.33 (d, J=2.3 Hz, 1H), 6.76-6.72 (m, 2H), 3.89 (s, 3H), 2.64 (s, 3H), 2.54 (s, br, 2H), 2.37-2.09 (m, 10H), 1.73-1.68 (m, 2H). ESI-MS m/z: 395.0 (M+H)+.

後処理

  1. customthe reaction mixture was partitioned into dichloromethane and saturated sodium bicarbonate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified on a RP-HPLC/MS purification system (Gradient
  6. waitacetonitrile in water, 25-95%, in 3.4 minutes with a cycle time of 5 min
  7. waitA shallow gradient between 25-50% of acetonitrile was used between 0.75-3.3 min
  8. customto separate
  9. washclose-eluting impurities

出典と根拠

ORDレコード
ord-5b2ef60b7f6f47c7af0fc92ef1a77ca7
出典データセット
uspto-grants-2014_05
特許番号
US08716284B2

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