Methylamine → Tert-butyl 3-(methylcarbamoyl)spiro[indene-1,4'-piperidine]-1'-carboxylate

HRID 2267110Notes

Reaction equation

HRID 2267110 reaction equation
CN.[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13]2([C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]([C:24](O)=[O:25])=[CH:16]2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].C[CH2:28][N:29]=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>C1COCC1.CN(C=O)C.O>[CH3:28][NH:29][C:24]([C:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:13]2([CH2:14][CH2:15][N:10]([C:8]([O:7][C:3]([CH3:6])([CH3:4])[CH3:5])=[O:9])[CH2:11][CH2:12]2)[CH:16]=1)=[O:25]

Participants

8

Reactant 4

HCID 6329MethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 497602001'-(Tert-butoxycarbonyl)spiro[indene-1,4'-piperidine]-3-carboxylic acid

Product 1

HCID 59600600Tert-butyl 3-(methylcarbamoyl)spiro[indene-1,4'-piperidine]-1'-carboxylateYield 84.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of methylamine in THF (2 mL) was added to a stirred solution of 1′-(tert-butyoxycarbonyl)spiro[indene-1,4′-piperidine]-3-carboxylic acid (C4) (0.51 g, 1.55 mmol), EDAC HCl (0.6 g, 3.00 mmol), HOBt (0.31 g ) in DMF (10 mL), and the solution was stirred at room temperature for 12 h. The solution was poured into water (50 mL), the aqueous layer was extracted with EtOAc (3×50 mL), dried, and concentrated under reduced pressure. The crude product was purified by Biotage SP1 on silica gel eluting with 12-100% EtOAc in hexanes to provide tert-butyl 3-(methylcarbamoyl)spiro[indene-1,4′-piperidine]-1′-carboxylate (C5) as a white solid (0.45 g). LC/MS (10-90% over 3 min with 0.9% FA) m/z 343 (M+1), Rt 3.0 minutes. 1HNMR (500 mHz, CDCl3) δ 7.73 (d, 1H), 7.23 (m, 3H), 7.14 (s, 1H), 6.05 (brm, 1H), 4.11 (m, 2H), 3.03 (m, 2H), 2.93 (d, 3H), 1.95 (m, 2H), 1.44 (s, 9H), 1.30 (m, 2H).

Workup

  1. extractionthe aqueous layer was extracted with EtOAc (3×50 mL)
  2. customdried
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by Biotage SP1 on silica gel eluting with 12-100% EtOAc in hexanes

Sources & evidence

ORD record
ord-4fdf0de2f401409c9cbc2d1caa1dfe58
Source dataset
uspto-grants-2010_12
Patent number
US07858790B2

Reaction notes

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