Pyridine → HCID 86683606, compound

HRID 1509204Notes

Reaction equation

HRID 1509204 reaction equation
[O:1]=[S:2]1(=[O:36])[NH:7][C:6]2[CH:8]=[C:9]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:10]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:21][CH2:20][CH2:19]4)=[CH:14][CH:13]=3)=[N:11][C:5]=2[O:4][CH2:3]1.[N:37]1[CH:42]=[CH:41][CH:40]=[C:39](B(O)O)[CH:38]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:25]([O:24][C:23](=[O:29])[NH:22][C:18]1([C:15]2[CH:16]=[CH:17][C:12]([C:10]3[C:9]([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)=[CH:8][C:6]4[N:7]([C:39]5[CH:38]=[N:37][CH:42]=[CH:41][CH:40]=5)[S:2](=[O:1])(=[O:36])[CH2:3][O:4][C:5]=4[N:11]=3)=[CH:13][CH:14]=2)[CH2:21][CH2:20][CH2:19]1)([CH3:28])([CH3:27])[CH3:26]

Participants

6

Reactant 3

HCID 1049Pyridine2×HCID 27343783-Pyridinylboronic acid2×HCID 123139090HCID 123139090, compound

Product 1

HCID 86683606HCID 86683606, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

In a 15 mL reaction tube was added tert-butyl (1-(4-(2,2-dioxido-7-phenyl-1H-pyrido[3,2-e][1,3,4]oxathiazin-6-yl)phenyl)cyclobutyl)carbamate (50 mg, 0.099 mmol), pyridin-3-ylboronic acid (24 mg, 0.197 mmol), copper(II)acetate (27 mg, 0.148 mmol) and 5 Å molecular sieves (30 mg) in anhydrous dichloromethane (1 ml). To this was added anhydrous pyridine (16 μl, 0.197 mmol) and the resulting black suspension stirred at room temperature under air for 24 hours. Further pyridine (1 mL) was added and the resulting black solution stirred at room temperature for 24 hours. Further pyridin-3-ylboronic acid (24 mg, 0.197 mmol) and copper (II)acetate (27 mg, 0.148 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 (40 mg 70% yield). 1H-NMR (500 MHz, CDCl3) δ 8.67-8.76 (2H, m), 7.89 (1H, d), 7.54 (1H, dd), 7.20-7.35 (7H, m), 7.06 (2H, d), 7.03 (1H, s), 5.38 (2H, s), 5.07 (1H, br s), 2.20-2.60 (4H, m), 2.00-2.15 (1H, m), 1.78-1.90 (1H, m), 1.10-1.50 (9H, br s). LCMS (Method A) RT=6.98 min, M+H+=584.99.

Workup

  1. customIn a 15 mL reaction tube
  2. stirringthe resulting black 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-d868df92ba474a2abe3c298e53f860c3
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

Loading…