Hydrochloric Acid → (3-Chloro-4-fluoro-phenyl)-(5,6,7,8-tetrahydro-9-thia-1,3,7-triaza-fluoren-4-yl)-amine

HRID 1887412Notes

Reaction equation

HRID 1887412 reaction equation
C(OC([N:8]1[CH2:20][C:19]2[S:18][C:17]3[N:16]=[CH:15][N:14]=[C:13](Cl)[C:12]=3[C:11]=2[CH2:10][CH2:9]1)=O)(C)(C)C.[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26].Cl.[OH-].[Na+]>CC(O)C.O1CCOCC1.ClCCl.CO.C(Cl)Cl>[Cl:22][C:23]1[CH:24]=[C:25]([NH:26][C:13]2[C:12]3[C:11]4[CH2:10][CH2:9][NH:8][CH2:20][C:19]=4[S:18][C:17]=3[N:16]=[CH:15][N:14]=2)[CH:27]=[CH:28][C:29]=1[F:30]

Participants

9

Reactant 4

HCID 313Hydrochloric Acid2×HCID 97083-Chloro-4-fluoroanilineHCID 14798Sodium HydroxideHCID 49788563tert-Butyl 4-chloro-5,6-dihydropyrido(4',3':4,5)thieno(2,3-d)pyrimidine-7(8H)-carboxylate

Product 1

HCID 58116889(3-Chloro-4-fluoro-phenyl)-(5,6,7,8-tetrahydro-9-thia-1,3,7-triaza-fluoren-4-yl)-amineYield 94%

Reagents, catalysts & solvents 4

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
82.5 °C

Procedure

To a mixture of 4-Chloro-5,8-dihydro-6H-9-thia-1,3,7-triaza-fluorene-7-carboxylic acid tert-butyl ester (6.86 g, 0.021 mol) and 3-chloro-4-fluoroaniline (3.2 g, 0.022 mol) in 2-propanol (96 ml) was added 4 N HCl in Dioxane (0.27 ml) and the mixture heated to 80-85° C. overnight. LCMS and TLC (5% MeOH/DCM) indicate that no SM (Boc-protected SM) present. 4 N HCl in Dioxane (10.5 ml, 0.042 mol) added and the heating continued until LCMS indicates no Boc-protected product present. Cooled to RT and conc. to dryness. The mixture was then suspended in dichloromethane (200 ml) and stirred with 1N NaOH (200 ml) for 30 min. Clear biphasic layers obtained. Layers separated and the aqueous washed with dichloromethane (100 ml). Combined organic layers washed with water (2×100 ml), then with brine (100 ml). Dried the organic layer with sodium sulfate, filtered and conc. to dryness. Dried under vacuum at to give 6.61 g (94%) of the product as indicated by LCMS and HNMR. 1H NMR (DMSO-d6) δ 8.41 (s, 1H), 8.24 (s, 1H), 7.92 (m, 1H), 7.64 (m, 1H), 7.39 (t, J=9.4 Hz, 1H), 3.94 (broad s, 1H), 3.32 (m, 2H), 3.05 (m, 2H), 3.01 (m, 2H); LCMS RT=2.13 min, [M+H]+=335.

Workup

  1. temperatureCooled to RT and conc. to dryness
  2. customobtained
  3. customLayers separated
  4. washthe aqueous washed with dichloromethane (100 ml)
  5. washCombined organic layers washed with water (2×100 ml)
  6. dry with materialDried the organic layer with sodium sulfate
  7. filtrationfiltered and conc. to dryness
  8. customDried under vacuum at

Sources & evidence

ORD record
ord-418ff332ac61448f90a13d9881e224b3
Source dataset
uspto-grants-2013_08
Patent number
US08501755B2

Reaction notes

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