Sodium Carbonate → 6-[({1-[2-(7-Fluoro-2-oxo-1(2H)-quinoxalinyl)ethyl]-4-piperidinyl}amino)methyl]-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one dihydrochloride

HRID 656944Notes

Reaction equation

HRID 656944 reaction equation
[ClH:1].Cl.[NH2:3][CH:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][N:12]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([F:22])[CH:20]=3)[N:15]=[CH:14][C:13]2=[O:23])[CH2:6][CH2:5]1.[O:24]=[C:25]1[CH2:30][S:29][C:28]2[CH:31]=[CH:32][C:33]([CH:35]=O)=[N:34][C:27]=2[NH:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>CO.O.C(N(CC)CC)C.C(Cl)(Cl)Cl>[ClH:1].[ClH:1].[F:22][C:19]1[CH:20]=[C:21]2[C:16]([N:15]=[CH:14][C:13](=[O:23])[N:12]2[CH2:11][CH2:10][N:7]2[CH2:6][CH2:5][CH:4]([NH:3][CH2:35][C:33]3[CH:32]=[CH:31][C:28]4[S:29][CH2:30][C:25](=[O:24])[NH:26][C:27]=4[N:34]=3)[CH2:9][CH2:8]2)=[CH:17][CH:18]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde2×HCID 688175421-[2-(4-amino-1-piperidinyl)ethyl]-7-fluoro-2(1H)-quinoxalinone dihydrochloride

Product 1

HCID 689926066-[({1-[2-(7-Fluoro-2-oxo-1(2H)-quinoxalinyl)ethyl]-4-piperidinyl}amino)methyl]-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one dihydrochloride

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6212ChloroformSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 1-[2-(4-amino-1-piperidinyl)ethyl]-7-fluoro-2(1H)-quinoxalinone dihydrochloride (60 mg; 0.166 mmol) and 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxaldehyde (for a synthesis, see WO2004058144, Example 7(d)) (32 mg, 0.166 mmol) in MeOH (3 ml), chloroform (3 ml) and triethylamine (0.06 ml) was stirred at rt for 1 h then heated at 70° C. overnight. It was cooled and sodium triacetoxyborohydride (0.106 g; 0.5 mmol) was added and the mixture was stirred at rt for 5 h. More 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde (4 mg) was added and the mixture was stirred for 3 h at rt. Sodium triacetoxyborohydride (53 mg) was added and the mixture was stirred at rt for 72 h. Water and sodium carbonate solution were added and the mixture was extracted (3×) with 10% MeOH-DCM, dried (sodium sulphate), evaporated, and chromatographed on silica gel, eluting with 0-15% MeOH-DCM to give the free base of the title compound.

Workup

  1. temperatureIt was cooled
  2. stirringthe mixture was stirred for 3 h at rt
  3. stirringthe mixture was stirred at rt for 72 h
  4. extractionthe mixture was extracted (3×) with 10% MeOH-DCM
  5. dry with materialdried (sodium sulphate)
  6. customevaporated
  7. customchromatographed on silica gel
  8. washeluting with 0-15% MeOH-DCM

Sources & evidence

ORD record
ord-b9b38b98608b4ee8a8a3df46f21369b0
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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