Triethylamine → HCID 86658429, compound

HRID 1968879Notes

Reaction equation

HRID 1968879 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C@@H:7]1[CH2:9][C@H:8]1[C:10]([OH:12])=O.C(Cl)(=O)C(Cl)=O.[Si:19]([O:26][C:27]1[CH:32]=[CH:31][C:30]([NH:33][CH2:34][C@@H:35]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[C@@H:36]([CH3:39])[CH2:37][CH3:38])=[CH:29][CH:28]=1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].C(N(CC)CC)C>CN(C=O)C.C(OCC)C.ClCCl>[Si:19]([O:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]([CH2:34][C@@H:35]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:44])([CH3:46])[CH3:45])[C@@H:36]([CH3:39])[CH2:37][CH3:38])[C:10]([C@@H:8]2[CH2:9][C@H:7]2[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)=[O:12])=[CH:29][CH:28]=1)([C:22]([CH3:23])([CH3:24])[CH3:25])([CH3:21])[CH3:20]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 39235822(1S,2S)-2-pyridin-2-ylcyclopropane-1-carboxylic acidHCID 67114485HCID 67114485, compound

Product 1

HCID 86658429HCID 86658429, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
35 °C

Procedure

A solution of trans-2-pyridin-2-yl-cyclopropylcarboxylic acid (270 mg, 1.7 mmol) and dichloromethane (15 mL) was treated with oxalyl chloride (170 μL, 2.0 mmol) and DMF (1 drop). The resulting reaction mixture was maintained at 35° C. for 3 h, then concentrated under reduced pressure to dryness. The residue was dissolved in dichloromethane (15 mL), and treated with tert-butyl (2S,3S)-1-(4-(tert-butyldimethylsilyloxy)phenylamino)-3-methylpentan-2-ylcarbamate (700 mg, 1.7 mmol) and triethylamine (690 μL, 5.0 mmol). The reaction mixture was maintained at room temperature overnight, then diluted with diethyl ether (30 mL) washed with saturated aqueous sodium bicarbonate (30 mL) and brine (30 mL), then dried over MgSO4, filtered and concentrated to afford a residue that was purified by column chromatography on silica gel (eluting with 15% ethyl acetate in hexanes) to afford tert-butyl (2S,3S)-1-(N-(4-(tert-butyldimethylsilyloxy)phenyl)-trans-2-(pyridin-2-yl)cyclopropanecarboxamido)-3-methylpentan-2-ylcarbamate (720 mg, 77% yield) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 8.04-8.13 (m, 1H), 7.25-7.36 (m, 1H), 6.91-7.00 (m, 1H), 6.87-6.91 (m, 1H), 6.76-6.86 (m, 2H), 6.55-6.62 (m, 1H), 6.46-6.55 (m, 1H), 4.83-4.98 (m, 1H), 4.15-4.27 (m, 1H), 3.45-3.64 (m, 1H), 2.81-2.93 (m, 1H), 2.23-2.48 (m, 1H), 1.68-1.81 (m, 1H), 1.37 (s, 3H), 1.29-1.52 (m, 2H), 1.28 (s, 3H), 1.25 (s, 3H), 1.15-1.22 (m, 1H), 0.86-0.97 (m, 1H), 0.78 (d, J=5.1 Hz, 9H), 0.67-0.71 (m, 3H), 0.60-0.67 (m, 3H), −0.06-0.02 (m, 6H); LRMS (ESI) m/e 568.3 [(M+H)+, calcd for C32H50N3O4Si 568.3].

Workup

  1. customThe resulting reaction mixture
  2. concentrationconcentrated under reduced pressure to dryness
  3. dissolutionThe residue was dissolved in dichloromethane (15 mL)
  4. temperatureThe reaction mixture was maintained at room temperature overnight
  5. washwashed with saturated aqueous sodium bicarbonate (30 mL) and brine (30 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford a residue that
  10. customwas purified by column chromatography on silica gel (eluting with 15% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-0c4d1bd6ef6a4990b11f161f7e1d3d5c
Source dataset
uspto-grants-2013_04
Patent number
US08426414B2

Reaction notes

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