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Trifluoroacetic acid → 1-[5-Nitroindole-2-carbonyl]-4-[3-(1,1-dimethylpropylamino)-2-pyridinyl]piperazine

HRID 2293767
Notes
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Reaction equation

HRID 2293767 reaction equation
CC(C)(O[C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13]2[C:18]([NH:19][C:20]([CH3:24])([CH3:23])[CH2:21][CH3:22])=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:9][CH2:8]1)=[O:6])C.FC(F)(F)C(O)=O.[OH-].[Na+].[N+:35]([C:38]1[CH:39]=[C:40]2[C:44](=[CH:45][CH:46]=1)[NH:43][C:42](C(O)=O)=[CH:41]2)([O-:37])=[O:36].C(N1C=CN=C1)(N1C=CN=C1)=O>C(Cl)Cl.O.O1CCCC1>[N+:35]([C:38]1[CH:39]=[C:40]2[C:44](=[CH:45][CH:46]=1)[NH:43][C:42]([C:5]([N:7]1[CH2:8][CH2:9][N:10]([C:13]3[C:18]([NH:19][C:20]([CH3:24])([CH3:23])[CH2:21][CH3:22])=[CH:17][CH:16]=[CH:15][N:14]=3)[CH2:11][CH2:12]1)=[O:6])=[CH:41]2)([O-:37])=[O:36]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 3512915-Nitroindole-2-carboxylic acidHCID 214776271-[1,1-Dimethylethoxycarbonyl]-4-[3-(1,1-dimethylpropylamino)-2-pyridinyl]piperazine

Product 1

HCID 21477599
1-[5-Nitroindole-2-carbonyl]-4-[3-(1,1-dimethylpropylamino)-2-pyridinyl]piperazine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-[1,1-dimethylethoxycarbonyl]-4-[3-(1,1-dimethylpropylamino)-2-pyridinyl]piperazine (PREPARATION 66, 4.99 g) in methylene chloride (75 ml) under nitrogen at 0° is added trifluoroacetic acid (14.3 ml) over 1 min. The resulting mixture is warmed to 20°-25°, stirred for 15 hrs, and then added to a solution of sodium hydroxide (7.44 g) in water (175 ml) at 0°. The layers are separated, the aqueous phase is extracted with methylene chloride (3×70ml), and the combined organic layer is washed with saline (60 ml), dried over sodium sulfate, and concentrated under reduced pressure to give the unprotected intermediate (Rf =0.14, TLC, methanol/chloroform, 10/90). In a flame-dried flask under nitrogen, 5-nitroindole-2-carboxylic acid (2.13 g) and 1,1'-carbonyldiimidazole (1.75 g) are dissolved in dry tetrahydrofuran and stirred for 3 hrs at 20°-25°. Then a solution of the intermediate (2.57 g) in dry tetrahydrofuran (3ml) is added and the resulting mixture is stirred for 1.8 days. The reaction mixture is filtered to give the title compound, NMR (dimethylsulfoxide-de) 12.41, 8.65, 8.09, 7.58, 7.16, 7.11, 6.91, 4.57, 3.93, 3.00, 1.71, 1.31 and 0.84. The filtrate is concentrated and is triturated with cold methanol to give an additional mount of the title compound.

Workup

  1. temperatureThe resulting mixture is warmed to 20°-25°
  2. customThe layers are separated
  3. extractionthe aqueous phase is extracted with methylene chloride (3×70ml)
  4. washthe combined organic layer is washed with saline (60 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give the unprotected intermediate (Rf =0.14, TLC, methanol/chloroform, 10/90)
  8. stirringstirred for 3 hrs at 20°-25°
  9. stirringthe resulting mixture is stirred for 1.8 days
  10. filtrationThe reaction mixture is filtered

Sources & evidence

ORD record
ord-0f2f1753b7024f589544132e1dc728e1
Source dataset
uspto-grants-1997_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05686610

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes