Acetic Acid → 3-[(1,4-cis)-4-(4-Quinolin-5-yl-piperazin-1-yl)-cyclohexyl]-1H-indole-5-carbonitrile

HRID 428562Notes

Reaction equation

HRID 428562 reaction equation
[N:1]1([C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[CH:9]=[CH:10][CH:11]=[N:12]3)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:17]([C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][CH:23]=[C:22]2[CH:28]1[CH2:33][CH2:32][C:31](=O)[CH2:30][CH2:29]1)#[N:18].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.Cl>ClC(Cl)C.CCOC(C)=O>[CH2:33]1[CH:28]([C:22]2[C:21]3[CH:20]=[C:19]([C:17]#[N:18])[CH:27]=[CH:26][C:25]=3[NH:24][CH:23]=2)[CH2:29][CH2:30][CH:31]([N:4]2[CH2:3][CH2:2][N:1]([C:7]3[C:8]4[CH:9]=[CH:10][CH:11]=[N:12][C:13]=4[CH:14]=[CH:15][CH:16]=3)[CH2:6][CH2:5]2)[CH2:32]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 5049666Sodium triacetoxyborohydrideHCID 106562265-(Piperazin-1-yl)quinolineHCID 112418863-(4-oxocyclohexyl)-1H-indole-5-carbonitrile

Product 1

HCID 251412183-[(1,4-cis)-4-(4-Quinolin-5-yl-piperazin-1-yl)-cyclohexyl]-1H-indole-5-carbonitrile

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-(1-piperazinyl)-quinoline (500 mg, 2.35 mmol), 4-(5-cyano-1H-3-indolyl)-cyclohexanone (540 mg, 2.35 mmol), and sodium triacetoxyborohydride (740 mg, 3.5 mmol) in dichloroethane (20 mL) was added acetic acid (0.27 mL, 4.7 mmol) and stirred overnight at room temperature. The reaction was quenched with 1 M NaOH (50 mL) and extracted in CH2Cl (3×100 mL). The organic fractions were combined, dried over Na2SO4, concentrated, filtered and chromatographed (5% MeOH/EtOAc) yielding 410 mg (41%) of the cis isomer as a white solid. The HCl salt was generated from EtOAc yielding a white solid: mp 220-223° C. Elemental Analysis for C28H29N5.HCl.1H2O; Calc'd C, 68.62; H, 6.58; N, 14.29; Found C, 68.99; H, 6.54; N, 14.06.

Workup

  1. customThe reaction was quenched with 1 M NaOH (50 mL)
  2. extractionextracted in CH2Cl (3×100 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. filtrationfiltered
  6. customchromatographed (5% MeOH/EtOAc)
  7. customyielding 410 mg (41%) of the cis isomer as a white solid

Sources & evidence

ORD record
ord-a0cbd1b2e1e14e7eb536ceb47fa21a5c
Source dataset
uspto-grants-2001_11
Patent number
US06313126B1

Reaction notes

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