4-Methylmorpholine → 4-[2-(3-Fluoro-2-methyl-benzyl)-3-phenyl-indolizine-1-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1963094Notes

Reaction equation

HRID 1963094 reaction equation
[F:1][C:2]1[C:3]([CH3:27])=[C:4]([CH:24]=[CH:25][CH:26]=1)[CH2:5][C:6]1[C:7]([C:21](O)=[O:22])=[C:8]2[N:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH:12]=[CH:11][CH:10]=[CH:9]2.[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C>[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][N:38]([C:21]([C:7]2[C:6]([CH2:5][C:4]3[CH:24]=[CH:25][CH:26]=[C:2]([F:1])[C:3]=3[CH3:27])=[C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:13]3[C:8]=2[CH:9]=[CH:10][CH:11]=[CH:12]3)=[O:22])[CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:29])[CH3:30]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 143452tert-Butyl piperazine-1-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 677747302-(3-Fluoro-2-methyl-benzyl)-3-phenyl-indolizine-1-carboxylic acid

Product 1

HCID 677724864-[2-(3-Fluoro-2-methyl-benzyl)-3-phenyl-indolizine-1-carbonyl]-piperazine-1-carboxylic acid tert-butyl esterYield 85.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the crude compound obtained in step 4 (125 mg, 0.35 mmol), 1-tert-butoxycarbonyl-piperazine (67.9 mg, 0.37 mmol), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (73.4 mg, 0.38 mmol) and 1-hydroxybenzotriazole (61.3 mg, 0.40 mmol) in DMF (2 ml) was added N-methyl-morpholine (0.115 ml, 1.04 mmol). The mixture was stirred at room temperature overnight, then quenched with water and extracted with EA. The organic layer was separated, dried over sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography (HEP/EA) to give 158 mg of the title compound.

Workup

  1. customquenched with water
  2. extractionextracted with EA
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by silica gel chromatography (HEP/EA)

Sources & evidence

ORD record
ord-b35b62629c9649289ce1f14c0245c87b
Source dataset
uspto-grants-2013_04
Patent number
US08415336B2

Reaction notes

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