Triethylamine → 1,1-dimethylethyl [4-({[(1S,2E)-4-(2,3-dihydro-1H-indol-1-yl)-1-(2-methylpropyl)-4-oxo-2-buten-1-yl]amino}carbonyl)tetrahydro-2H-pyran-4-yl]carbamate

HRID 78742Notes

Reaction equation

HRID 78742 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:50])/[CH:42]=[CH:43]/[C@@H:44]([NH2:49])[CH2:45][CH:46]([CH3:48])[CH3:47])[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34][CH2:33]1.[C:51]([O:55][C:56]([NH:58][C:59]1([C:65](O)=[O:66])[CH2:64][CH2:63][O:62][CH2:61][CH2:60]1)=[O:57])([CH3:54])([CH3:53])[CH3:52].CCN(CC)CC>C(Cl)Cl>[N:32]1([C:41](=[O:50])/[CH:42]=[CH:43]/[C@@H:44]([NH:49][C:65]([C:59]2([NH:58][C:56](=[O:57])[O:55][C:51]([CH3:53])([CH3:52])[CH3:54])[CH2:60][CH2:61][O:62][CH2:63][CH2:64]2)=[O:66])[CH2:45][CH:46]([CH3:48])[CH3:47])[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 86704317[(1S,2E)-4-(2,3-dihydro-1H-indol-1-yl)-1-(2-methylpropyl)-4-oxo-2-buten-1-yl]amine trifluoroacetate

Product 1

HCID 867043181,1-dimethylethyl [4-({[(1S,2E)-4-(2,3-dihydro-1H-indol-1-yl)-1-(2-methylpropyl)-4-oxo-2-buten-1-yl]amino}carbonyl)tetrahydro-2H-pyran-4-yl]carbamateYield 31.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 50 wt % ®T3P in EtOAc (1.2 mL, 2.016 mmol) was added dropwise to a solution of [(1S,2E)-4-(2,3-dihydro-1H-indol-1-yl)-1-(2-methylpropyl)-4-oxo-2-buten-1-yl]amine trifluoroacetate (500 mg, 1.343 mmol), 4-((tert-butoxycarbonyl)amino)tetrahydro-2H-pyran-4-carboxylic acid (329 mg, 1.343 mmol), and Et3N (0.93 mL, 6.71 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 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 204 mg (31%) of the title compound. LC-MS m/z 486 (M+H)+, 1.07 min (ret time).

Workup

  1. customThe ice bath was removed
  2. washthe reaction 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-9e289ca0e33b40e3be12dec9097e015f
Source dataset
uspto-grants-2014_09
Patent number
US08841463B2

Reaction notes

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