Acetic Acid → HCID 66604600, compound

HRID 2410782Notes

Reaction equation

HRID 2410782 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([C:23]([O:25][CH3:26])=[O:24])[C:11]3[NH:12][C:13]4[CH:14]=[C:15]([CH:21]=O)[CH:16]=[CH:17][C:18]=4[C:19]=3[N:20]=2)[CH:5]=[CH:6][CH:7]=1.[C:27]([N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1)([CH3:30])([CH3:29])[CH3:28].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>CN(C=O)C.C(Cl)Cl>[C:27]([N:31]1[CH2:36][CH2:35][N:34]([CH2:21][C:15]2[CH:16]=[CH:17][C:18]3[C:19]4[N:20]=[C:8]([C:4]5[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=5)[CH:9]=[C:10]([C:23]([O:25][CH3:26])=[O:24])[C:11]=4[NH:12][C:13]=3[CH:14]=2)[CH2:33][CH2:32]1)([CH3:30])([CH3:29])[CH3:28]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 35305721-Tert-butylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 86663034HCID 86663034, compound

Product 1

HCID 66604600HCID 66604600, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of methyl 2-(3-chlorophenyl)-7-formyl-5H-pyrido[3,2-b]indole-4-carboxylate (80 mg, 0.22 mmol) in DMF (1 mL) was stirred for 5 min and then diluted with DCM (10 mL). 1-tert-butylpiperazine (38 mg, 0.26 mmol) was added and the suspension was cooled in an ice bath. Sodium triacetoxyborohydride (125 mg, 0.592 mmol) was added and the suspension was left stirring for 0.5 hr. Acetic acid (0.025 mL, 0.44 mmol) was then added and the bath removed. The reaction was left stirring at RT overnight, diluted with DCM, and washed with sat. aq. NaHCO3 solution followed by water (2×). After drying with sodium sulfate, the solvent was removed and radial chromatography (step gradient elution with DCM containing 0 to 3% MeOH) afforded methyl 7-((4-tert-butylpiperazin-1-yl)methyl)-2-(3-chlorophenyl)-5H-pyrido[3,2-b]indole-4-carboxylate (45 mg, 0.092 mmol, 42% yield) as a yellow solid. MS (ESI) m/z 491.19 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 9.49 (1H, s), 8.36 (1H, d, J=7.94 Hz), 8.24 (1H, s), 8.20 (1H, s), 8.04 (1H, d, J=7.63 Hz), 7.53 (1H, t, J=7.78 Hz), 7.35-7.39 (1H, m), 7.33 (1H, d, J=7.93 Hz), 4.09 (3H, s), 3.70 (2H, s), 2.63 (8H, br. s.), 1.07 (9H, s).

Workup

  1. temperaturethe suspension was cooled in an ice bath
  2. waitthe suspension was left
  3. stirringstirring for 0.5 hr
  4. customthe bath removed
  5. waitThe reaction was left
  6. stirringstirring at RT overnight
  7. additiondiluted with DCM
  8. washwashed with sat. aq. NaHCO3 solution
  9. dry with materialAfter drying with sodium sulfate
  10. customthe solvent was removed
  11. washradial chromatography (step gradient elution with DCM containing 0 to 3% MeOH)

Sources & evidence

ORD record
ord-348a7f5fafd643789d51b82e4cf69571
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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