1,2-Dichloroethane → 6-tert-butyl-2-(3-{5-[5-(1,1-dimethyl-2-morpholin-4-yl-2-oxo-ethyl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl}-2-hydroxymethyl-phenyl)-8-fluoro-2H-phthalazin-1-one

HRID 2069724노트

반응식

HRID 2069724 반응식
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[C:18]([CH2:44][OH:45])=[C:19]([C:23]3[CH:24]=[C:25]([NH:31][C:32]4[N:37]=[CH:36][C:35]([C:38]([CH3:43])([CH3:42])[C:39](O)=[O:40])=[CH:34][CH:33]=4)[C:26](=[O:30])[N:27]([CH3:29])[CH:28]=3)[CH:20]=[CH:21][CH:22]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[NH:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1.C(Cl)CCl.[Cl-].[NH4+]>CN(C1C=CN=CC=1)C.C(Cl)Cl.C(OCC)(=O)C>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]3[CH:24]=[C:25]([NH:31][C:32]4[CH:33]=[CH:34][C:35]([C:38]([CH3:43])([CH3:42])[C:39]([N:46]5[CH2:51][CH2:50][O:49][CH2:48][CH2:47]5)=[O:40])=[CH:36][N:37]=4)[C:26](=[O:30])[N:27]([CH3:29])[CH:28]=3)[C:18]=1[CH2:44][OH:45])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2]

참가 물질

8

반응물 4

HCID 111,2-DichloroethaneHCID 8083MorpholineHCID 25517Ammonium ChlorideHCID 469088042-(6-{5-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-2-oxo-1,2-dihydro-pyridin-3-ylamino}-pyridin-3-yl)-2-methyl-propionic acid

생성물 1

HCID 469088056-tert-butyl-2-(3-{5-[5-(1,1-dimethyl-2-morpholin-4-yl-2-oxo-ethyl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl}-2-hydroxymethyl-phenyl)-8-fluoro-2H-phthalazin-1-one수율 74%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

2-(6-{5-[3-(6-tert-Butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-2-oxo-1,2-dihydro-pyridin-3-ylamino}-pyridin-3-yl)-2-methyl-propionic acid (50 mg, 0.08 mmol), morpholine (11 mg, 0.12 mmol), EDC (23 mg, 0.12 mmol), and DMAP (15 mg, 0.12 mmol) were dissolved in 1 ml of DCM and stirred at room temperature under nitrogen overnight. Ethyl acetate and saturated aqueous ammonium chloride were added and the layers were separated. The organic layer was washed with dilute ammonium chloride, then saturated aqueous sodium bicarbonate, dried, and concentrated. The crude product was purified by flash chromatography using a gradient of 0% to 10% methanol in DCM to give 40 mg (74%) of 6-tert-butyl-2-(3-{5-[5-(1,1-dimethyl-2-morpholin-4-yl-2-oxo-ethyl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl}-2-hydroxymethyl-phenyl)-8-fluoro-2H-phthalazin-1-one. MS: (M+H)+=681. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.43 (s, 9 H) 1.53 (s, 6 H) 3.45 (br. s, 7 H) 3.71 (s, 3 H) 3.76 (br. s., 1H) 4.41 (br. s., 2 H) 6.85 (d, J=8.69 Hz, 1 H) 7.31-7.43 (m, 3 H) 7.48-7.61 (m, 4 H) 7.96 (s, 1 H) 8.15 (s, 1 H) 8.30 (s, 1 H) 8.69 (s, 1 H).

후처리

  1. customthe layers were separated
  2. washThe organic layer was washed with dilute ammonium chloride
  3. dry with materialsaturated aqueous sodium bicarbonate, dried
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography

출처 및 근거

ORD 기록
ord-6a2a270749644b0cab8bdfcd0cda3273
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08299077B2

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