Pyridine → HCID 49830279, compound

HRID 2088996Notes

Reaction equation

HRID 2088996 reaction equation
[CH:1]1([NH:7][C:8]2[NH:13][C:12](=O)[CH:11]=[C:10]([C:15]3[C:23]4[C:18](=[N:19][CH:20]=[CH:21][CH:22]=4)[NH:17][CH:16]=3)[N:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.P(Cl)(Cl)([Cl:26])=O.N1C=CC=CC=1>>[Cl:26][C:12]1[CH:11]=[C:10]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[CH:21][CH:22]=3)[NH:17][CH:16]=2)[N:9]=[C:8]([NH:7][CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[N:13]=1

Participants

4

Reactant 3

HCID 1049PyridineHCID 24813Phosphorus oxychlorideHCID 135962806HCID 135962806, compound

Product 1

HCID 49830279HCID 49830279, compoundYield 25.5%

Procedure

A mixture of Example 49d (100 mg, 0.323 mmol), phosphoryl trichloride (1 ml, 10.92 mmol) and pyridine (0.05 ml, 0.618 mmol) was stirred at room temperature for 4 hours. The reaction mixture was concentrated in vacuo and purified by HPLC on a Phenomenex Luna C8(2) 5 μm 100 Å AXIA column (30 mm×75 mm), eluting with a gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B), at a flow rate of 50 mL/min (0-0.5 min 10% A, 0.5-7.0 min linear gradient 10-95% A, 7.0-10.0 min 95% A, 10.0-12.0 min linear gradient 95-10% A) to give the title product (27 mg, 25.5% yield). MS (ESI) m/e 328 (M+H)+; 1H NMR (400 MHz, DMSO-d6) ppm 1.15-1.48 (m, 5H) 1.58-1.69 (m, 1H) 1.73-1.83 (m, J=9.31, 3.51 Hz, 2H) 1.94-2.03 (m, 2H) 3.76-3.90 (m, 1H) 6.93-7.04 (m, 1H) 7.07 (s, 1H) 7.17 (dd, J=7.93, 4.58 Hz, 1H) 8.28 (d, J=3.36 Hz, 1H) 8.34 (s, 1H) 8.79 (d, J=7.63 Hz, 1H) 12.01 (s, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. custompurified by HPLC on a Phenomenex Luna C8(2) 5 μm 100 Å AXIA column (30 mm×75 mm)
  3. washeluting with a gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B), at a flow rate of 50 mL/min (0-0.5 min 10% A, 0.5-7.0 min linear gradient 10-95% A, 7.0-10.0 min 95% A, 10.0-12.0 min linear gradient 95-10% A)

Sources & evidence

ORD record
ord-a20f8f2c2e3e4d5c987a1e075dd2c688
Source dataset
uspto-grants-2013_05
Patent number
US08435980B2

Reaction notes

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