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 2069724Notes

Reaction equation

HRID 2069724 reaction equation
[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]

Participants

8

Reactant 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

Product 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-oneYield 74%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-6a2a270749644b0cab8bdfcd0cda3273
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

Loading…