Methylamine → HCID 68324069, compound

HRID 573621Notes

Reaction equation

HRID 573621 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[CH:17]=[C:16]([CH3:18])[N:15]=[C:14]3[S:19][C:20]([C:30]([OH:32])=O)=[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=4)[C:13]=23)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.[CH3:39][NH2:40].C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[CH:17]=[C:16]([CH3:18])[N:15]=[C:14]3[S:19][C:20]([C:30]([NH:40][CH3:39])=[O:32])=[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=4)[C:13]=23)(=[O:9])=[O:10])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6329MethylamineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 68324148HCID 68324148, compound

Product 1

HCID 68324069HCID 68324069, compoundYield 54.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

In an dried round bottom flask was added 4-{[(3-chlorophenyl)sulfonyl]amino}-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine-2-carboxylic acid (50 mg, 0.102 mmol) (Example 35), DCM (1 mL), oxalyl chloride (0.013 mL, 0.153 mmol) and DMF (10 μL). The resulting mixture was stirred at RT for 10 min. Methylamine (2M in THF) (0.256 mL, 0.511 mmol) was then added dropwise and the mixture stirred at RT for 30 min. Aqueous NaHCO3 solution (25 mL) and DCM (25 mL) were then added and the organic layer separated. The aqueous was re-extracted with DCM (2×20 mL) and the combined organics washed with brine (30 mL), dried and concentrated. Purification by chromatography on silica gel, eluting with a gradient of 0-10% MeOH in DCM was followed by further purification by chromatography on silica gel, eluting with a gradient of 20-50% ethyl acetate in DCM, to give the title compound (28 mg). LCMS (A) m/z: 502 [M+1]+, Rt 1.21 min (acidic), Rt 0.91 min (basic).

Workup

  1. stirringthe mixture stirred at RT for 30 min
  2. customthe organic layer separated
  3. extractionThe aqueous was re-extracted with DCM (2×20 mL)
  4. washthe combined organics washed with brine (30 mL)
  5. customdried
  6. concentrationconcentrated
  7. customPurification by chromatography on silica gel
  8. washeluting with a gradient of 0-10% MeOH in DCM
  9. customwas followed by further purification by chromatography on silica gel
  10. washeluting with a gradient of 20-50% ethyl acetate in DCM

Sources & evidence

ORD record
ord-6b98608ff259431990edd63ad06cf36e
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

Loading…