Diisopropylethylamine → HCID 178496556, compound

HRID 2042411Notes

Reaction equation

HRID 2042411 reaction equation
CO[C:3](=[O:12])[CH2:4][C@H:5]1[CH2:9][CH2:8][C@H:7]([O:10][CH3:11])[CH2:6]1.O([Si](C)(C)C)[K].Cl.Cl.Cl.[O:22]1[C:30]2[CH:29]=[CH:28][N:27]=[C:26]([N:31]3[CH2:36][CH2:35][N:34]([CH2:37][CH2:38][C@H:39]4[CH2:44][CH2:43][C@H:42]([NH2:45])[CH2:41][CH2:40]4)[CH2:33][CH2:32]3)[C:25]=2[CH:24]=[CH:23]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C([O-])(O)=O.[Na+]>C(Cl)Cl>[O:22]1[C:30]2[CH:29]=[CH:28][N:27]=[C:26]([N:31]3[CH2:36][CH2:35][N:34]([CH2:37][CH2:38][C@H:39]4[CH2:44][CH2:43][C@H:42]([NH:45][C:3](=[O:12])[CH2:4][C@H:5]5[CH2:9][CH2:8][C@H:7]([O:10][CH3:11])[CH2:6]5)[CH2:41][CH2:40]4)[CH2:33][CH2:32]3)[C:25]=2[CH:24]=[CH:23]1

Participants

8

Reactant 6

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59598533Racemic trans-(3-methoxy-cyclopentyl)-acetic acid methyl esterHCID 178478592HCID 178478592, compound2×HCID 178504318HCID 178504318, compound

Product 1

HCID 178496556HCID 178496556, compoundYield 78.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of racemic trans-(3-methoxy-cyclopentyl)-acetic acid methyl ester [WO 2009/019174] (70 mg, 0.41 mmol) and KOSiMe3 (88 mg, 0.69 mmol) in CH2Cl2 (1.5 ml) was stirred at room temperature over night. The solvent was evaporated and DMF (1.5 ml) was added followed by trans-4-[2-(4-furo[3,2-c]pyridin-4-yl-piperazin-1-yl)-ethyl]-cyclohexylamine trihydrochloride (intermediate A) (150 mg, 0.34 mmol), DIPEA (177 mg, 1.37 mmol) and TBTU (143 mg, 0.44 mmol). After stirring 4 h at room temperature, sat. aq. NaHCO3 sol. was added and the product was extracted with CH2Cl2. The organic layer was dried (Na2SO4), the solvent was evaporated and the crude product was purified by flash chromatography on silica gel (CH2Cl2/MeOH/25% NH3 aq 140:10:1) to yield the title compound as a white solid (125 mg, 78%), MS (ISP) m/z=469.3 [(M+H)+].

Workup

  1. customThe solvent was evaporated
  2. additionDMF (1.5 ml) was added
  3. stirringAfter stirring 4 h at room temperature
  4. extractionthe product was extracted with CH2Cl2
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. customthe solvent was evaporated
  7. customthe crude product was purified by flash chromatography on silica gel (CH2Cl2/MeOH/25% NH3 aq 140:10:1)

Sources & evidence

ORD record
ord-55e76aa2526440e1b2b10e0f032d7df8
Source dataset
uspto-grants-2013_11
Patent number
US08586579B2

Reaction notes

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