Diisopropylethylamine → HCID 178496555, compound

HRID 1260708Notes

Reaction equation

HRID 1260708 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.[S:22]1[C:26]2=[C:27]([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)[N:28]=[CH:29][CH:30]=[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>[CH3:11][O:10][C@H:7]1[CH2:8][CH2:9][C@H:5]([CH2:4][C:3]([NH:45][C@H:42]2[CH2:43][CH2:44][C@H:39]([CH2:38][CH2:37][N:34]3[CH2:35][CH2:36][N:31]([C:27]4[N:28]=[CH:29][CH:30]=[C:25]5[CH:24]=[CH:23][S:22][C:26]=45)[CH2:32][CH2:33]3)[CH2:40][CH2:41]2)=[O:12])[CH2:6]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 178478591HCID 178478591, compound2×HCID 178504318HCID 178504318, compound

Product 1

HCID 178496555HCID 178496555, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of racemic trans-(3-methoxy-cyclopentyl)-acetic acid methyl ester [WO 2009/019174] (41 mg, 0.24 mmol) and KOSiMe3 (51 mg, 0.40 mmol) in CH2Cl2 (1 ml) was stirred at room temperature over night. The solvent was evaporated and DMF (1 ml) was added followed by trans-4-[2-(4-thieno[2,3-c]pyridin-7-yl-piperazin-1-yl)-ethyl]-cyclohexylamine trihydrochloride (intermediate A; 90 mg, 0.20 mmol), DIPEA (103 mg, 0.80 mmol) and TBTU (83 mg, 0.26 mmol). After stirring 3 h at room temperature, sat. aq. NaHCO3 sol. was added and the product was extracted with CH2Cl2. The organic layer was dried (MgSO4), the solvent was evaporated and the crude product was purified by flash chromatography on silica gel (CH2Cl2/MeOH 95:5) to yield the title compound as a light red foam (65 mg, 68%), MS (ISP) m/z=485.4 [(M+H)+].

Workup

  1. customThe solvent was evaporated
  2. additionDMF (1 ml) was added
  3. stirringAfter stirring 3 h at room temperature
  4. extractionthe product was extracted with CH2Cl2
  5. dry with materialThe organic layer was dried (MgSO4)
  6. customthe solvent was evaporated
  7. customthe crude product was purified by flash chromatography on silica gel (CH2Cl2/MeOH 95:5)

Sources & evidence

ORD record
ord-60bdb4b885c44507b3258f7a923d8004
Source dataset
uspto-grants-2013_06
Patent number
US08470828B2

Reaction notes

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