Diisopropylethylamine → (R)-tert-Butyl 4-(3-(2-chlorobenzamido)-N-methyl-2,3-dihydro-1H-indene-5-carboxamido)piperidine-1-carboxylate

HRID 1193423Notes

Reaction equation

HRID 1193423 reaction equation
C[CH2:2][N:3]([CH:7]([CH3:9])C)[CH:4]([CH3:6])[CH3:5].CN(C([O:17]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:34][C:35]1[CH:55]=[CH:54][CH:53]=[CH:52][C:36]=1[C:37]([NH:39][C@H:40]1[C:48]2[C:43](=[CH:44][CH:45]=C(C(O)=O)[CH:47]=2)[CH2:42][CH2:41]1)=[O:38].CNC1C[CH2:62][N:61]([C:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[CH2:60]C1>C1COCC1>[Cl:34][C:35]1[CH:55]=[CH:54][CH:53]=[CH:52][C:36]=1[C:37]([NH:39][C@H:40]1[C:48]2[C:43](=[CH:44][CH:45]=[C:9]([C:7]([N:3]([CH:4]3[CH2:5][CH2:62][N:61]([C:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[CH2:60][CH2:6]3)[CH3:2])=[O:17])[CH:47]=2)[CH2:42][CH2:41]1)=[O:38]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 15380702tert-Butyl 4-(methylamino)piperidine-1-carboxylateHCID 59505489(3R)-3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid

Product 1

HCID 66805453(R)-tert-Butyl 4-(3-(2-chlorobenzamido)-N-methyl-2,3-dihydro-1H-indene-5-carboxamido)piperidine-1-carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

DIPEA (0.28 ml, 1.585 mmol, 2.5 eq) and HATU (240 mg, 0.634 mmol, 1 eq) were added to a suspension, cooled to 0° C., of (3R)-3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (E-01) (200 mg, 0.634 mmol, 1 eq) in THF (5 ml). The reaction mixture was stirred for 15 min, and then a solution of tert-butyl 4-(methylamino)piperidine-1-carboxylate (135 mg, 0.634 mmol, 1 eq) in THF (3 ml) was added and stirring was carried out for 16 h at room temperature. The reaction mixture was concentrated under reduced pressure, diluted with dichloromethane (50 ml) and washed with saturated ammonium chloride solution (30 ml), water (30 ml) and saturated sodium chloride solution (30 ml). Drying over sodium sulfate and concentration under reduced pressure were then carried out. The crude product was purified by column chromatography (silica gel, 2% methanol/dichloromethane) to yield the desired product in the form of a white solid. Yield: 92% (300 mg, 0.587 mmol)

Workup

  1. stirringstirring
  2. waitwas carried out for 16 h at room temperature
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additiondiluted with dichloromethane (50 ml)
  5. washwashed with saturated ammonium chloride solution (30 ml), water (30 ml) and saturated sodium chloride solution (30 ml)
  6. dry with materialDrying over sodium sulfate and concentration under reduced pressure
  7. customThe crude product was purified by column chromatography (silica gel, 2% methanol/dichloromethane)

Sources & evidence

ORD record
ord-9fa6303b1fc54ad490cf2b0346844e3e
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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