Pyridine → 1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-6-morpholino-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

HRID 1025625Notes

Reaction equation

HRID 1025625 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[N:12]=[C:11]3[NH:13][CH:14]=[C:15]([C:16]#[N:17])[C:10]3=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[C:18]([C:22]1[CH:23]=[C:24]2[C:29](=[C:30]([F:32])[CH:31]=1)[C:28](=[O:33])[N:27]([C:34]1[C:42]3[CH2:41][O:40]B(O)[C:38]=3[CH:37]=[CH:36][CH:35]=1)[N:26]=[CH:25]2)([CH3:21])([CH3:20])[CH3:19].N1C=CC=CC=1.[NH4+].[Cl-]>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCCl>[C:18]([C:22]1[CH:23]=[C:24]2[C:29](=[C:30]([F:32])[CH:31]=1)[C:28](=[O:33])[N:27]([C:34]1[C:42]([CH2:41][OH:40])=[C:38]([N:13]3[C:11]4=[N:12][C:7]([N:4]5[CH2:5][CH2:6][O:1][CH2:2][CH2:3]5)=[CH:8][CH:9]=[C:10]4[C:15]([C:16]#[N:17])=[CH:14]3)[CH:37]=[CH:36][CH:35]=1)[N:26]=[CH:25]2)([CH3:21])([CH3:19])[CH3:20]

Participants

7

Reactant 4

HCID 1049PyridineHCID 25517Ammonium ChlorideHCID 710081996-tert-butyl-8-fluoro-2-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-4-yl)phthalazin-1(2H)-oneHCID 710082926-morpholino-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

Product 1

HCID 710083931-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-6-morpholino-1H-pyrrolo[2,3-b]pyridine-3-carbonitrileYield 99.7%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
45 °C

Procedure

In a 25 mL round-bottomed flask, 6-morpholino-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (65 mg, 285 μmol, Eq: 1.00), 6-tert-butyl-8-fluoro-2-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-4-yl)phthalazin-1(2H)-one (150 mg, 427 μmol, Eq: 1.5) and copper acetate (69.8 mg) were combined with 1,2-dichloroethane (3 ml) to give a blue suspension. Pyridine (45.1 mg, 46.1 μl, 570 μmol, Eq: 2) was added. The reaction mixture was heated to 45° C. and stirred for 2 d. The reaction mixture was poured into 20 mL sat NH4Cl and extracted with EtOAc (3×20 mL). The organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 5% to 10% MeOH in DCM, then silica gel, 12 g, 30% to 45% EtOAc in hexanes) gave 1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-6-morpholino-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (157 mg, 50%) as colorless oil which foams upon being dried.

Workup

  1. customto give a blue suspension
  2. additionThe reaction mixture was poured into 20 mL
  3. extractionextracted with EtOAc (3×20 mL)
  4. dry with materialThe organic layers were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (silica gel, 40 g, 5% to 10% MeOH in DCM

Sources & evidence

ORD record
ord-170a6d507c7d4f7885f6b48fbcb32c80
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

Loading…