Triethylamine → (S,E)-tert-butyl (4-((6-(indolin-1-yl)-6-oxohex-4-en-3-yl)carbamoyl)tetrahydro-2H-pyran-4-yl)carbamate

HRID 78736Notes

Reaction equation

HRID 78736 reaction equation
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCOC(C)=O.FC(F)(F)C(O)=O.[N:32]1([C:41](=[O:48])/[CH:42]=[CH:43]/[C@@H:44]([NH2:47])[CH2:45][CH3:46])[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34][CH2:33]1.[C:49]([O:53][C:54]([NH:56][C:57]1([C:63](O)=[O:64])[CH2:62][CH2:61][O:60][CH2:59][CH2:58]1)=[O:55])([CH3:52])([CH3:51])[CH3:50].CCN(CC)CC>C(Cl)Cl>[N:32]1([C:41](=[O:48])/[CH:42]=[CH:43]/[C@@H:44]([NH:47][C:63]([C:57]2([NH:56][C:54](=[O:55])[O:53][C:49]([CH3:51])([CH3:50])[CH3:52])[CH2:58][CH2:59][O:60][CH2:61][CH2:62]2)=[O:64])[CH2:45][CH3:46])[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34][CH2:33]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 111923Propylphosphonic anhydrideHCID 12682194-(Boc-amino)tetrahydropyran-4-carboxylic acidHCID 86704314[(1S,2E)-4-(2,3-dihydro-1H-indol-1-yl)-1-ethyl-4-oxo-2-buten-1-yl]amine trifluoroacetate

Product 1

HCID 86704316(S,E)-tert-butyl (4-((6-(indolin-1-yl)-6-oxohex-4-en-3-yl)carbamoyl)tetrahydro-2H-pyran-4-yl)carbamateYield 38%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 50 wt % ®T3P in EtOAc (1.3 mL, 2.184 mmol) was added dropwise to a solution of [(1S,2E)-4-(2,3-dihydro-1H-indol-1-yl)-1-ethyl-4-oxo-2-buten-1-yl]amine trifluoroacetate (500 mg, 1.452 mmol), 4-((tert-butoxycarbonyl)amino)tetrahydro-2H-pyran-4-carboxylic acid (356 mg, 1.452 mmol), and Et3N (1 mL, 7.21 mmol) in CH2Cl2 (5 mL) at 0° C. (bath temp). The ice bath was removed, and the reaction was stirred at RT. After 1 h 20 min, the reaction mixture was washed with saturated aq. NaHCO3 (1×5 mL) and 10% citric acid (1×5 mL). The organic layer was concentrated under a stream of nitrogen, and the residue was purified by flash column chromatography, giving 251 mg (38%) of the title compound. LC-MS m/z 458 (M+H)+, 0.96 (ret time).

Workup

  1. customThe ice bath was removed
  2. washthe reaction mixture was washed with saturated aq. NaHCO3 (1×5 mL) and 10% citric acid (1×5 mL)
  3. concentrationThe organic layer was concentrated under a stream of nitrogen
  4. customthe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-0cec782f97f941f0aa0a19b8a8f351f3
Source dataset
uspto-grants-2014_09
Patent number
US08841463B2

Reaction notes

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