Pyridine → HCID 59310834, compound

HRID 1841909Notes

Reaction equation

HRID 1841909 reaction equation
[NH2:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][CH:7]([P:18](=[O:27])([O:23][CH2:24][CH:25]=[CH2:26])[O:19][CH2:20][CH:21]=[CH2:22])[P:8](=[O:17])([O:13][CH2:14][CH:15]=[CH2:16])[O:9][CH2:10][CH:11]=[CH2:12])=[CH:4][CH:3]=1.N1C=CC=CC=1.[Br:36][CH2:37][C:38](Br)=[O:39]>C(Cl)Cl>[Br:36][CH2:37][C:38]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH:7]([P:18](=[O:27])([O:23][CH2:24][CH:25]=[CH2:26])[O:19][CH2:20][CH:21]=[CH2:22])[P:8](=[O:17])([O:13][CH2:14][CH:15]=[CH2:16])[O:9][CH2:10][CH:11]=[CH2:12])=[CH:28][CH:29]=1)=[O:39]

Participants

5

Reactant 3

HCID 1049PyridineHCID 61147Bromoacetyl bromideHCID 86641294HCID 86641294, compound

Product 1

HCID 59310834HCID 59310834, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of aminobenzyl bisphosphonate 27 (180 mg, 0.41 mmol) in CH2Cl2 (5 mL) at 0° C. was added pyridine (49 μL, 0.61 mmol) followed by bromoacetylbromide (35 μL, 0.41 mmol). The reaction mixture was stirred at 0° C. for 30 min and at room temperature for another 2.5 h. The reaction mixture was diluted with CH2Cl2, washed with aqueous 1N HCl solution, saturated NaHCO3 solution, and saturated NaCl solution, then dried over MgSO4, filtered and concentrated. The crude product was purified by flash chromatography on silica gel using a gradient of 0-10% MeOH in CH2Cl2 as eluant to provide bromide 28 as a clear yellow oil (175 mg, 3.11×10−4 mol, 76%). 1H NMR (400 MHz, CDCl3) δ 2.72 (tt, J=23.9, 6.2 Hz, 1H), 3.26 (dt, J=16.3, 6.1 Hz, 2H), 4.02 (s, 2H), 4.48-4.62 (m, 8H), 5.20-5.24 (m, 4H), 5.29-5.35 (m, 4H), 5.83-5.94 (m, 4H), 7.25-7.28 (m, 2H), 7.42-7.46 (m, 2H), 8.11 (bs, 1H).

Workup

  1. washwashed with aqueous 1N HCl solution, saturated NaHCO3 solution, and saturated NaCl solution
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography on silica gel using a gradient of 0-10% MeOH in CH2Cl2 as eluant

Sources & evidence

ORD record
ord-d3ad0af2880b410ca83025a25de74437
Source dataset
uspto-grants-2015_02
Patent number
US08946144B2

Reaction notes

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