4-Methylmorpholine → 3-(1-Pyrrolidin-1-ylindan-5-yl)propynoic acid-(4'-chlorobiphenyl-4-yl)amide

HRID 735031Notes

Reaction equation

HRID 735031 reaction equation
[N:1]1([CH:6]2[C:14]3[C:9](=[CH:10][C:11]([C:15]#[C:16][C:17](O)=[O:18])=[CH:12][CH:13]=3)[CH2:8][CH2:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN1CCOCC1.ClC(OCC(C)C)=O.[Cl:35][C:36]1[CH:41]=[CH:40][C:39]([C:42]2[CH:47]=[CH:46][C:45]([NH2:48])=[CH:44][CH:43]=2)=[CH:38][CH:37]=1>C1COCC1.ClCCl>[Cl:35][C:36]1[CH:37]=[CH:38][C:39]([C:42]2[CH:47]=[CH:46][C:45]([NH:48][C:17](=[O:18])[C:16]#[C:15][C:11]3[CH:10]=[C:9]4[C:14](=[CH:13][CH:12]=3)[CH:6]([N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[CH2:7][CH2:8]4)=[CH:44][CH:43]=2)=[CH:40][CH:41]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 86754-Amino-4'-chlorodiphenylHCID 62365Isobutyl chloroformateHCID 68817830(1-pyrrolidin-1-ylindan-5-yl)propynoic Acid

Product 1

HCID 578458263-(1-Pyrrolidin-1-ylindan-5-yl)propynoic acid-(4'-chlorobiphenyl-4-yl)amide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.1 g (0.39 mmol) of (1-pyrrolidin-1-ylindan-5-yl)propynoic acid and 47 mL (0.43 mmol) of N-methylmorpholine in 5 mL of absolute THF is combined with 56 mL (0.43 mmol) of isobutyl chloroformate at −15° C. and stirred for ten minutes. Then 87 mg (0.43 mmol) of 4′-chlorobiphenyl-4-ylamine are added at ambient temperature and the reaction mixture is stirred for 14 hours. Then 3 mL of dichloromethane are added to the reaction mixture and this is stirred for 48 hours. Then the reaction mixture is filtered, the filtrate is evaporated down, combined with water and extracted with dichloromethane. The organic phase is evaporated down. The purification is carried out by preparative HPLC (eluant: dichloromethane/methanol/ammonia=8:2:0.2). Yield: 9 mg (5.7% of theory); C28H25ClN2O (M=440.97); calc.: molecular ion peak (M+H)+: 441/443; found: molecular ion peak (M+H)+: 441/443.

Workup

  1. stirringthe reaction mixture is stirred for 14 hours
  2. stirringthis is stirred for 48 hours
  3. filtrationThen the reaction mixture is filtered
  4. customthe filtrate is evaporated down
  5. extractionextracted with dichloromethane
  6. customThe organic phase is evaporated down
  7. customThe purification

Sources & evidence

ORD record
ord-64650fb27cab4cff868ecdc8f02998ed
Source dataset
uspto-grants-2009_09
Patent number
US07592373B2

Reaction notes

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