2,2,6,6-Tetramethylpiperidine → HCID 86706147, compound

HRID 2176298Notes

Reaction equation

HRID 2176298 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([NH:14][C:15]([C@@H:17]3[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:27])[C@@H:24]([NH2:26])[CH3:25])[NH:18]3)=[O:16])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1.[C:28]([CH:31]([O:36][C:37](=[O:43])[C:38]([CH3:42])([CH3:41])[CH:39]=[CH2:40])[CH:32]1[CH2:35][O:34][CH2:33]1)(O)=[O:29].CC1(C)CCCC(C)(C)N1.F[P-](F)(F)(F)(F)F.C(C(=NO[C+](N(C)C)N1CCOCC1)C(OCC)=O)#N>CN(C)C=O.ClCCl>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([NH:14][C:15]([C@@H:17]3[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:27])[C@@H:24]([NH:26][C:28]([CH:31]([O:36][C:37](=[O:43])[C:38]([CH3:42])([CH3:41])[CH:39]=[CH2:40])[CH:32]4[CH2:35][O:34][CH2:33]4)=[O:29])[CH3:25])[NH:18]3)=[O:16])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 130352,2,6,6-TetramethylpiperidineHCID 86706144HCID 86706144, compoundHCID 86706146HCID 86706146, compoundHCID 178472143HCID 178472143, compound

Product 1

HCID 86706147HCID 86706147, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A stirred solution of (S)-1-((S)-2-amino-propionyl)-hexahydro-pyridazine-3-carboxylic acid [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-amide (141 mg, 0.618 mmol) and 2,2-dimethyl-but-3-enoic acid carboxy-oxetan-3-yl-methyl ester (315 mg, 0.725 mmol) in anhydrous N,N-dimethylformamide (10 mL) was cooled to 0° C. under nitrogen. 2,2,6,6-Tetramethylpiperidine (261 mg, 313 μL, 1.85 mmol) was added, rapidly followed by (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate (371 mg, 0.865 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 15 h. The reaction mixture was diluted with dichloromethane and washed with saturated ammonium chloride solution (2×), saturated sodium bicarbonate solution (2×), the organic layer was filtered through a phase-separator and evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 1:0 to 0:1 to give the title compound (167 mg, 42%) as a yellow/brown foam and as an approximate 1:1 mixture of diastereoisomers. LCMS (m/z) 644.2, 646.1[M+H], Tr=2.63 min.

Workup

  1. washwashed with saturated ammonium chloride solution (2×), saturated sodium bicarbonate solution (2×)
  2. filtrationthe organic layer was filtered through a phase-separator
  3. customevaporated
  4. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-ade14bc13d72466c9b37879833c51c9c
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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