Pyridine → HCID 67256553, compound

HRID 1509206Notes

Reaction equation

HRID 1509206 reaction equation
[O:1]=[C:2]1[CH2:7][O:6][C:5]2[N:8]=[C:9]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:27][CH2:26][CH2:25]4)=[CH:20][CH:19]=3)[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:11][C:4]=2[NH:3]1.[N:36]1[CH:41]=[CH:40][CH:39]=[C:38](B(O)O)[CH:37]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[O:1]=[C:2]1[CH2:7][O:6][C:5]2[N:8]=[C:9]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:32])([CH3:34])[CH3:33])[CH2:25][CH2:26][CH2:27]4)=[CH:20][CH:19]=3)[C:10]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[CH:11][C:4]=2[N:3]1[C:38]1[CH:37]=[N:36][CH:41]=[CH:40][CH:39]=1

Participants

6

Reactant 3

HCID 1049Pyridine2×HCID 27343783-Pyridinylboronic acid2×HCID 67256382HCID 67256382, compound

Product 1

HCID 67256553HCID 67256553, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

In a 15 mL reaction tube was added tert-butyl 1-(4-(2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutylcarbamate (100 mg, 0.212 mmol), pyridin-3-ylboronic acid (52 mg, 0.424 mmol), copper(II)acetate (58 mg, 0.318 mmol) and 5 Å molecular sieves (60 mg) in anhydrous dichloromethane (2 ml). To this was added anhydrous pyridine (34 μl, 0.424 mmol) and the resulting blue suspension stirred at room temperature under air for 24 hours. Further pyridine (1 mL) was added and the resulting deep blue solution stirred at room temperature for 24 hours. Further pyridin-3-ylboronic acid (52 mg, 0.424 mmol) and copper(II)acetate (58 mg, 0.318 mmol) were added and the mixture stirred at room temperature for 72 hours. The reaction mixture was concentrated to dryness under reduced pressure and the residue purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 88:12 to 0:100) to give the desired product as an off-white solid (32 mg 28% yield). 1H-NMR (500 MHz, CDCl3) δ 8.50-8.80 (2H, br m), 7.71 (1H, d), 7.50 (1H, br s), 7.09-7.26 (7H, m), 6.92-7.02 (2H, d), 6.71 (1H, s), 5.00 (3H, s), 2.10-2.55 (4H, m), 1.92-2.05 (1H, m), 1.66-1.80 (1H, m), 1.00-1.45 (9H, br m). LCMS (Method A) RT=6.61 min, M+H+=549.09.

Workup

  1. customIn a 15 mL reaction tube
  2. stirringthe resulting deep blue solution stirred at room temperature for 24 hours
  3. stirringthe mixture stirred at room temperature for 72 hours
  4. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
  5. customthe residue purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 88:12 to 0:100)

Sources & evidence

ORD record
ord-2da3dee097a74255b284c6d6c76a9362
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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