Triethylamine → Tert-butyl 9-[2-(isobutylcarbamoylamino)acetyl]-4,9-diazaspiro[5.5]-undecane-4-carboxylate

HRID 2284865Notes

Reaction equation

HRID 2284865 reaction equation
Cl.C1[C:7]2(C[CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)CNCC1.[CH2:20]([NH:24][C:25]([NH:27][CH2:28][C:29]([OH:31])=O)=[O:26])[CH:21]([CH3:23])[CH3:22].C(N(CC)CC)C.CN(C(ON1N=N[C:49]2[CH:50]=[CH:51][CH:52]=[N:53][C:48]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O.C(OCC)(=O)C.CN(C)C=O>[CH2:20]([NH:24][C:25]([NH:27][CH2:28][C:29]([N:53]1[CH2:48][CH2:49][C:50]2([CH2:7][CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH2:11]2)[CH2:51][CH2:52]1)=[O:31])=[O:26])[CH:21]([CH3:22])[CH3:23]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 16785937(Isobutylcarbamoyl)glycineHCID 71464197Tert-butyl 2,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride

Product 1

HCID 118022279Tert-butyl 9-[2-(isobutylcarbamoylamino)acetyl]-4,9-diazaspiro[5.5]-undecane-4-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a round bottom flask add tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (1.38 mmol), 2-(isobutylcarbamoylamino)acetic acid (1.15 mmol), dimethylformamide (3.8 mL), triethylamine (1.72 mmol) and HATU (1.26 mmol. Stir at room temperature for 16 hours, then dilute with water (50 mL) and ethyl acetate (50 mL). Wash the organic phase with concentrated ammonium chloride (50 mL) and brine (50 mL). Dry the organics over sodium sulfate, filter, and concentrate under reduced pressure. Purify the intermediate by flash chromatography (40 g silica gel cartridge) eluting with 0-10% methanol in ethyl acetate to yield tert-butyl 9-[2-(isobutylcarbamoylamino)acetyl]-4,9-diazaspiro[5.5]undecane-4-carboxylate (0.38 g, 0.93 mmol): MS (m/z): 411.2 (M+H).

Workup

  1. washWash the organic phase with concentrated ammonium chloride (50 mL) and brine (50 mL)
  2. dry with materialDry the organics over sodium sulfate
  3. filtrationfilter
  4. concentrationconcentrate under reduced pressure
  5. customPurify the intermediate by flash chromatography (40 g silica gel cartridge)
  6. washeluting with 0-10% methanol in ethyl acetate

Sources & evidence

ORD record
ord-f0b629ee13954bd28965925c3b5605b4
Source dataset
uspto-grants-2015_09
Patent number
US09145437B2

Reaction notes

Loading…