Hydrochloric Acid → HCID 67373322, 화합물

HRID 2168725노트

반응식

HRID 2168725 반응식
[ClH:1].Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:30][CH:31]2[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[C:17]([NH:19][C:20](=[O:22])[CH3:21])[CH:18]=1)[CH2:4][CH2:5][CH3:6].[CH:38](=O)[CH:39]([CH3:41])[CH3:40].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([Cl:60])(=O)C.CCN(C(C)C)C(C)C.Cl>C(Cl)Cl.C(O)(=O)C.O.CCOC(C)=O.CN(C1C=CN=CC=1)C.CCOCC>[ClH:60].[ClH:1].[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:30][CH:31]2[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[C:17]([N:19]([CH2:38][CH:39]([CH3:41])[CH3:40])[C:20](=[O:22])[CH3:21])[CH:18]=1)[CH2:4][CH2:5][CH3:6]

참가 물질

12

반응물 6

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 6561IsobutyraldehydeHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 67373992HCID 67373992, 화합물

생성물 1

HCID 67373322HCID 67373322, 화합물수율 33.6%

시약·촉매·용매 5

HCID 176Acetic Acid촉매HCID 142844-(Dimethylamino)pyridine촉매HCID 3283Diethyl Ether용매HCID 6344Dichloromethane용매2회HCID 22728543Water ethylacetate용매

실험 절차

To a solution of 5-[3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-phenylamine (Example 62, 0.2 mmol, 88 mg) in DCM (2.0 mL) was added isobutyraldehyde (0.3 mmol, 28 μL), and 1 drop of acetic acid. Then sodium triacetoxyborohydride (0.6 mmol, 127 mg) was added. The mixture was stirred at room temperature for 1 hour then condensed. The mixture was then diluted with water/EtOAc. The solvent was removed in vacuo and the residue was again dissolved in DCM (2.0 mL) at 0° C., added acetyl chloride (0.4 mmol, 29 μL), DIEA (0.6 mmol, 105 μL) and DMAP (5 mg). And the mixture was stirred at room temperature for 1 hour. It was then condensed in vacuo and the residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH) to give a colorless sticky solid, which was dissolved in DCM (1.0 mL), 2N HCl in ether (1.0 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (41 mg). LCMS: m/z 537 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.40-7.43 (1 H, m), 7.28-7.35 (2 H, m), 7.07 (1 H, s), 5.52 (1 H, bs), 4.53-4.59 (1 H, m), 3.65-3.71 (1 H, m), 3.29-3.47 (7 H, m), 2.92-2.97 (2 H, m), 2.89 (3 H, s), 2.18-2.37 (4 H, m), 1.99-2.07 (2 H, m), 1.84 (3 H, s), 1.25-1.83 (9 H, m), 1.18-1.26 (2 H, m), 0.91-0.95 (6 H, m), 0.80 (3 H, t).

후처리

  1. customcondensed
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was again dissolved in DCM (2.0 mL) at 0° C.
  4. stirringAnd the mixture was stirred at room temperature for 1 hour
  5. customcondensed in vacuo
  6. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 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-d8ed326e9719413b96c30a36a06253c5
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09045461B2

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