Hydrochloric Acid → HCID 67386579, 화합물

HRID 1971905노트

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HRID 1971905 반응식
[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]

참가 물질

13

반응물 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, 화합물

생성물 1

HCID 67386579HCID 67386579, 화합물수율 95.9%

시약·촉매·용매 6

HCID 176Acetic Acid용매2회HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 21892291Methanol tetrahydrofuran water용매HCID 22728543Water ethylacetate용매2회

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온도
100 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-7a42211582624862821d7a188b570df0
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431575B2

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