Triethylamine → HCID 10367877, compound

HRID 1725349Notes

Reaction equation

HRID 1725349 reaction equation
C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.[NH2:15][CH2:16][CH2:17][CH2:18][N:19]1[CH2:23][CH:22]([C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[C:31]([O:34][CH3:35])[N:32]=3)[N:27]=[CH:26][CH:25]=2)[O:21][C:20]1=[O:36].C(N(CC)CC)C.[O:44]=[C:45]1[CH2:50][S:49][C:48]2[CH:51]=[CH:52][C:53]([CH:55]=O)=[N:54][C:47]=2[NH:46]1.[BH4-].[Na+]>C(Cl)Cl.CO.C(Cl)(Cl)Cl>[CH3:35][O:34][C:31]1[N:32]=[C:33]2[C:28](=[CH:29][CH:30]=1)[N:27]=[CH:26][CH:25]=[C:24]2[CH:22]1[O:21][C:20](=[O:36])[N:19]([CH2:18][CH2:17][CH2:16][NH:15][CH2:55][C:53]2[CH:52]=[CH:51][C:48]3[S:49][CH2:50][C:45](=[O:44])[NH:46][C:47]=3[N:54]=2)[CH2:23]1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 4311764Sodium borohydrideHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 68840513HCID 68840513, compound

Product 1

HCID 10367877HCID 10367877, compoundYield 53.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To the dihydrochloride salt of 3-(3-Amino-propyl)-5-(6-methoxy-[1,5]naphthyridin-4-yl)-oxazolidin-2-one (previous patent) (0.47 g, 1.25 mmol) in CH2Cl2 (14 mL) and MeOH (3.5 mL) was added triethylamine (1.0 mL, 7.2 mmol) and the mixture was stirred at room temperature until all the solid went into solution. 3-Oxo-3,4-dihydro-2H-pyrido[3,2,b][1,4]thiazine-6-carbaldehyde (SB-735214, 0.24 g, 1.24 mmol) was added and the reaction mixture was stirred for 15 hours. Sodium borohydride (0.0519, 1.35 mmol) was added followed by methanol (10 mL). After 30 minutes, the reaction mixture was diluted with chloroform and washed with saturated aqueous NaHCO3 solution, dried (MgSO4), filtered and concentrated. Flash chromatography on silica gel using a gradient of 0-10% MeOH/CHCl3 afforded the product as a white solid (0.32 g, 53%) 1H NMR (400 MHz, CDCl3): δ8.80 (d, J=4.6 Hz, 1H); 8.36 (d, J=9.1 Hz, 1H); 7.70 (d, J=4.5 Hz, 1H); 7.56 (d, J=7.8 Hz, 1H); 7.17 (d, J=9.1 Hz, 1H); 6.92 (d, J=7.8 Hz, 1H); 6.31 (dd, J=8.6, 6.9 Hz, 1H); 4.35 (t, J=9.3 Hz, 1H); 4.04 (s, 3H); 3.75 (s, 2H); 3.48 (s, 2H); 3.47 (dd, J=8.9, 6.9 Hz, 1H); 3.41 (m, 2H); 2.63 (m, 2H), 1.75 (m, 2H). MS (ES) m/e 481 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred for 15 hours
  2. washwashed with saturated aqueous NaHCO3 solution
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-9241bf4c5aa64444b81e2481e21cd425
Source dataset
uspto-grants-2009_02
Patent number
US07491714B2

Reaction notes

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