1,2-Dichloroethane → HCID 11948360, compound

HRID 885687Notes

Reaction equation

HRID 885687 reaction equation
[F:1][C:2]1[C:12]([C:13]([OH:15])=O)=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][S:9][C:4]=2[CH:3]=1.[C:16]1([N:26]2[CH:34]=[C:33]3[C:28]([CH2:29][CH2:30][CH:31]([NH2:35])[CH2:32]3)=[N:27]2)[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][CH:17]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C.CCOC(C)=O.[OH-].[Na+]>[C:16]1([N:26]2[CH:34]=[C:33]3[C:28]([CH2:29][CH2:30][CH:31]([NH:35][C:13]([C:12]4[C:2]([F:1])=[CH:3][C:4]5[S:9][CH2:8][C:7](=[O:10])[NH:6][C:5]=5[CH:11]=4)=[O:15])[CH2:32]3)=[N:27]2)[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][CH:17]=1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 21873817HCID 21873817, compoundHCID 59560622HCID 59560622, compound

Product 1

HCID 11948360HCID 11948360, compoundYield 8.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 7-fluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid (17 mg, 0.076 mmol), 2-naphthalen-1-yl-4,5,6,7-tetrahydro-2H-indazol-5-ylamine (18 mg, 0.069 mmol), and HOBT (24.0 mg, 0.103 mmol) in DMF (1 mL) was added EDC (20.0 mg, 0.103 mmol). The reaction mixture was stirred overnight at RT. The reaction was diluted with EtOAc (10 mL) and 1 N NaOH (5 mL). The aqueous layer was extracted with EtOAc (3×10 mL). The combined organic layers were washed with 1 N HCl (10 mL), brine (10 mL), dried (MgSO4), filtered, and concentrated. The crude was purified by acidic reverse phase HPLC. The TFA salt of the title compound was diluted in CH3OH (10 mL) and treated with anionic exchange resin (550 Å, OH). The mixture was stirred at RT for 20 min. The mixture was filtered and the filtrate was concentrated to afford 2.8 mg (8%) of the title compound. MS (ESI): exact mass calculated for C26H21FN4O2S, 472.14; m/z found, 473.3 [M+H]+. 1H NMR (500 MHz, CDCl3): 8.76 (br s, 1H), 7.91-7.84 (m, 4H), 7.54-7.49 (m, 5H), 7.11 (d, J=11.4, 1H), 6.97-6.92 (m, 1H), 4.73-4.71 (m, 1H), 3.46 (s, 2H), 3.20 (dd, J=15.5, 5.0, 1H), 3.08-3.02 (m, 1H), 3.00-2.94 (m, 1H), 2.74 (dd, J=15.5, 7.0, 1H), 2.26-2.22 (m, 1H), 2.17-2.11 (m, 1H).

Workup

  1. extractionThe aqueous layer was extracted with EtOAc (3×10 mL)
  2. washThe combined organic layers were washed with 1 N HCl (10 mL), brine (10 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was purified by acidic reverse phase HPLC
  7. additionThe TFA salt of the title compound was diluted in CH3OH (10 mL)
  8. additiontreated with anionic exchange resin (550 Å, OH)
  9. stirringThe mixture was stirred at RT for 20 min
  10. filtrationThe mixture was filtered
  11. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-f67253bbb5b344f0a817ee840fa39120
Source dataset
uspto-grants-2012_08
Patent number
US08242275B2

Reaction notes

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