Hydrochloric Acid → HCID 67386579、化合物

HRID 2168627ノート

反応式

HRID 2168627 の反応式
[ClH:1].Cl.C([O:5][C:6](=O)[CH2:7][CH2:8][N:9]1[CH2:14][CH2:13][CH:12]([O:15][C:16]2[N:17]=[N:18][C:19]([CH2:35][CH2:36][CH2:37][CH3:38])=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)=[CH:24][CH:23]=3)[CH:21]=2)[CH2:11][CH2:10]1)C.[Li+].[OH-].Cl.[CH3:43][NH:44][CH3:45].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl>C1COCC1.CO.O.O.CCOC(C)=O.C(O)(=O)C.CN(C=O)C.C(Cl)Cl.CCOCC>[ClH:1].[ClH:1].[CH2:35]([C:19]1[N:18]=[N:17][C:16]([O:15][CH:12]2[CH2:11][CH2:10][N:9]([CH2:8][CH2:7][C:6]([N:44]([CH3:45])[CH3:43])=[O:5])[CH2:14][CH2:13]2)=[CH:21][C:20]=1[C:22]1[CH:23]=[CH:24][C:25]([O:28][CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)=[CH:26][CH:27]=1)[CH2:36][CH2:37][CH3:38]

参加物

13

反応物 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 10473Dimethylamine, hydrochlorideHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67373658HCID 67373658、化合物

生成物 1

HCID 67386579HCID 67386579、化合物収率 95.9%

試薬・触媒・溶媒 6

HCID 176Acetic Acid溶媒2 回HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 21892291Methanol tetrahydrofuran water溶媒HCID 22728543Water ethylacetate溶媒2 回

反応条件

温度
100 °C

実験手順

To a solution of 3-{4-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-piperidin-1-yl}-propionic acid ethyl ester dihydrochloride (Example 15, 1.0 mmol, 583 mg) in THF-MeOH—H2O (1:1:1, 3 mL) was added LiOH (20 mmol, 480 mg). The mixture was stirred at 100° C. for 10 min. The mixture was then diluted with water/EtOAc and neutralized with acetic acid. The organic layers combined, dried, and condensed in vacuo, and the residue was dissolved in DMF (2 mL). Dimethylamine hydrochloride (3.0 mmol, 245 mg), HBTU (3.0 mmol, 1.14 g), DIEA (3.0 mmol, 0.53 mL) were added to the mixture, and the mixture was stirred at 100° C. for 2 hours. It was then diluted with water/EtOAc and neutralized with acetic acid. The organic layers were combined, dried, and condensed in vacuo, and the residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH) to give a colorless sticky solid, which was dissolved in DCM (2 mL), 2N HCl in ether (2 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (279 mg). LCMS: m/z 510 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.31-7.35 (2H, m), 7.01-7.07 (3H, m), 5.46-5.52 (1H, m), 4.37-4.43 (1H, m), 3.35-3.50 (5H, m), 3.03 (6H, s), 2.87-2.95 (5H, m), 2.20-2.35 (4H, m), 1.96-2.03 (2H, m), 1.78-1.84 (2H, m), 1.27-1.63 (8H, m), 1.20-1.24 (2H, m), 0.80 (3H, t).

後処理

  1. customdried
  2. customcondensed in vacuo
  3. stirringthe mixture was stirred at 100° C. for 2 hours
  4. customdried
  5. customcondensed in vacuo
  6. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH)
  7. customto give a colorless sticky solid, which
  8. waitkept at room temperature for 10 min
  9. customcondensed
  10. customtriturated with hexanes

出典と根拠

ORDレコード
ord-b228ba93b8d4461d9d85cdbd3e74726e
出典データセット
uspto-grants-2015_06
特許番号
US09045461B2

反応ノート

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