Triethylamine → racemic trans 3-[3-(6-benzenesulfonyl-6H-1,2,3,5,6-pentaaza-as-indacen-1-yl)-cyclopentyl]-1-methyl-1-(2,2,2-trifluoro-ethyl)-urea

HRID 1257693Notes

Reaction equation

HRID 1257693 reaction equation
[C:1]1([S:7]([N:10]2[CH:21]=[CH:20][C:19]3[C:11]2=[N:12][CH:13]=[C:14]2[C:18]=3[N:17]([CH:22]3[CH2:26][CH2:25][CH:24]([NH2:27])[CH2:23]3)[N:16]=[N:15]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.ClC(Cl)(O[C:39](=[O:45])OC(Cl)(Cl)Cl)Cl.Cl.[CH3:48][NH:49][CH2:50][C:51]([F:54])([F:53])[F:52]>C(Cl)Cl>[C:1]1([S:7]([N:10]2[CH:21]=[CH:20][C:19]3[C:11]2=[N:12][CH:13]=[C:14]2[C:18]=3[N:17]([C@H:22]3[CH2:26][CH2:25][C@H:24]([NH:27][C:39](=[O:45])[N:49]([CH3:48])[CH2:50][C:51]([F:54])([F:53])[F:52])[CH2:23]3)[N:16]=[N:15]2)(=[O:8])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 22496068Methyl(2,2,2-trifluoroethyl)amine hydrochlorideHCID 67324681HCID 67324681, compound

Product 1

HCID 131730646racemic trans 3-[3-(6-benzenesulfonyl-6H-1,2,3,5,6-pentaaza-as-indacen-1-yl)-cyclopentyl]-1-methyl-1-(2,2,2-trifluoro-ethyl)-ureaYield 38.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A mixture of 3-(6-benzene sulfonyl-6H-1,2,3,5,6-pentaaza-as-indacen-1-yl)cyclopentylamine (200 mg, 520 μmol) and triethylamine (333 μL, 2.39 mmol) in DCM (3 mL) was added dropwise to a stirred solution of triphosgene (121 mg, 400 μmol) in DCM (3 mL) and stirred at ambient temperature for 1 hour. A solution of the free base of methyl (2,2,2-trifluoroethyl) amine hydrochloride (240 mg, 1.60 mmol) in DCM (2 mL) was added dropwise and after 1 hour the reaction was quenched with a saturated solution of sodium bicarbonate. After standing for 2 days and organic phase was dried using a phase separator cartridge and purified by column chromatography on silica gel (gradient: 0 to 100% ethyl acetate in cyclohexane) to afford 80 mg (29%) of racemic trans 3-[3-(6-benzenesulfonyl-6H-1,2,3,5,6-pentaaza-as-indacen-1-yl)-cyclopentyl]-1-methyl-1-(2,2,2-trifluoro-ethyl)-urea as a gum. LCMS (Method B, ESI): RT=3.70 min, m+H=522.4.

Workup

  1. customwas quenched with a saturated solution of sodium bicarbonate
  2. waitAfter standing for 2 days
  3. customorganic phase was dried
  4. custompurified by column chromatography on silica gel (gradient: 0 to 100% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-abcc79364e7a425681eea1e870a67e44
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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