Piconol → HCID 86616994, compound

HRID 1944584Notes

Reaction equation

HRID 1944584 reaction equation
[Cl:1][C:2]1[C:3]([NH:40][S:41]([CH3:44])(=[O:43])=[O:42])=[N:4][C:5]([N:30]([CH2:36][CH2:37][O:38][CH3:39])[CH2:31][C@@H:32]2[CH2:34][C@H:33]2[CH3:35])=[CH:6][C:7]=1[C:8]1[O:12][C:11]([C@@:13]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:21])[CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:10][N:9]=1.O[CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][N:48]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:3]([N:40]([S:41]([CH3:44])(=[O:42])=[O:43])[CH2:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][N:48]=2)=[N:4][C:5]([N:30]([CH2:36][CH2:37][O:38][CH3:39])[CH2:31][C@@H:32]2[CH2:34][C@H:33]2[CH3:35])=[CH:6][C:7]=1[C:8]1[O:12][C:11]([C@@:13]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28])([CH3:21])[CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:10][N:9]=1

Participants

6

Reactant 4

HCID 11474PiconolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 86616995HCID 86616995, compound2×

Product 1

HCID 86616994HCID 86616994, compoundYield 47.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of tert-butyl (1R)-1-(5-{3-chloro-6-((2-methoxyethyl){[trans-2-methylcyclopropyl]methyl}amino)-2-[(methylsulfonyl)amino]pyridin-4-yl}-1,3,4-oxadiazol-2-yl)-1-methyl-2-phenylethylcarbamate (intermediate 8.4.2, 0.028 g, 0.043 mmol) in toluene (1 ml) at 0 oC was added 2-(hydroxymethyl)pyridine (0.004 ml, 0.043 mmol) and triphenylphosphine (0.011 g, 0.043 mmol) followed by diisopropyl azodicarboxylate (0.008 ml, 0.043 mmol). The ice bath was removed and the solution stirred at room temperature overnight. The next day the solution was concentrated in vacuo, taken up in DMF and filtered. The product was purified by reverse phase HPLC affording 0.015 g of tert-butyl (1R)-1-(5-{3-chloro-6-((2-methoxyethyl){[trans-2-methylcyclopropyl]methyl}amino)-2[(methylsulfonyl)(pyridin-2-ylmethyl)amino]pyridin-4-yl}-1,3,4-oxadiazol-2-yl)-1-methyl-2-phenylethylcarbamate LCMS [M+H]740.2.

Workup

  1. customThe ice bath was removed
  2. concentrationThe next day the solution was concentrated in vacuo
  3. filtrationfiltered
  4. customThe product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-9cfae98c36ce42b2a000ddb7f6510125
Source dataset
uspto-grants-2013_03
Patent number
US08394837B2

Reaction notes

Loading…