Cyclopentanone → HCID 16743931, compound

HRID 1993611Notes

Reaction equation

HRID 1993611 reaction equation
[C:1]1(=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.BrBr.[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([C@:16]([NH:38][C:39]([NH2:41])=[S:40])([C:24]2[CH:29]=[C:28]([O:30][C:31]([F:36])([F:35])[CH:32]([F:34])[F:33])[CH:27]=[C:26]([F:37])[CH:25]=2)[CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:14][CH:15]=1>CCO>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([C@:16]([NH:38][C:39]2[S:40][C:1]3[CH2:5][CH2:4][CH2:3][C:2]=3[N:41]=2)([C:24]2[CH:29]=[C:28]([O:30][C:31]([F:35])([F:36])[CH:32]([F:33])[F:34])[CH:27]=[C:26]([F:37])[CH:25]=2)[CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[N:14][CH:15]=1

Participants

5

Reactant 3

HCID 8452CyclopentanoneHCID 24408BromineHCID 58897156HCID 58897156, compound

Product 1

HCID 16743931HCID 16743931, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of cyclopentanone (68 mg, 0.8 mmol) in EtOH (1 ml) was added Br2 (15 mg, 0.09 mmol) at r.t., sealed and stirred for 5 mins. The yellow solution became clear colorless. (R)-1-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)thiourea (20 mg, 0.04 mmol) was added to the reaction mixture and the mixture was heated at 75° C. for 16 hrs, then heated at 160° C. under microwave for 30 mins. The reaction mixture was purified by prep HPLC, desired fraction condensed under vacuum to give (R)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-5,6-dihydro-4H-cyclopenta[d]thiazol-2-amine (6 mg, 27% yield). LCMS: 3.67 min [M+1] 566.40 (4 min gradient, MeOH/H2O 0.1% TFA); 1H NMR (400 MHz, CD3OD) δ ppm 2.32-2.42 (m, 2H), 2.55-2.66 (m, 2H), 2.69-2.80 (m, 2H), 3.88 (d, J=13.14 Hz, 1H), 4.28 (d, J=13.39 Hz, 1H), 6.27 (t, J=50.0 Hz, 1H), 6.61 (d, J=6.82 Hz, 2H), 6.97-7.09 (m, 4H), 7.24 (s, 1H) 7.34 (ddd, J=9.98, 2.02, 1.89 Hz, 1H), 7.41 (d, J=8.59 Hz, 1H) 7.79 (dd, J=8.59, 2.53 Hz, 1H), 8.38 (d, J=2.02 Hz, 1H).

Workup

  1. customsealed
  2. temperatureheated at 160° C. under microwave for 30 mins
  3. customThe reaction mixture was purified by prep HPLC
  4. customdesired fraction condensed under vacuum

Sources & evidence

ORD record
ord-94ecf47062794132add984c9f0e05a9c
Source dataset
uspto-grants-2010_01
Patent number
US07652023B2

Reaction notes

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