(5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-nitrophenyl carbonate → (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ((S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-(2-hydroxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-yl)carbamate

HRID 339084Notes

Reaction equation

HRID 339084 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C@H:7]([C:12]2[CH:13]=[CH:14][C:15]3[N:16]([C:18]([C:21]4[CH:30]=[CH:29][C:28]5[C:23](=[CH:24][C:25]([O:32][CH2:33][CH2:34][OH:35])=[C:26]([F:31])[CH:27]=5)[N:22]=4)=[N:19][N:20]=3)[CH:17]=2)[C:8]([F:11])([F:10])[F:9])[CH2:3]1.[C:36](=O)([O:46]C1C=CC([N+]([O-])=O)=CC=1)[O:37][CH2:38][C:39]1[O:40][C:41](=[O:45])[O:42][C:43]=1[CH3:44]>CN(C=O)C>[F:10][C:8]([F:9])([F:11])[C@H:7]([N:4]1[CH2:5][CH2:6][C@H:2]([NH:1][C:36](=[O:46])[O:37][CH2:38][C:39]2[O:40][C:41](=[O:45])[O:42][C:43]=2[CH3:44])[CH2:3]1)[C:12]1[CH:13]=[CH:14][C:15]2[N:16]([C:18]([C:21]3[CH:30]=[CH:29][C:28]4[C:23](=[CH:24][C:25]([O:32][CH2:33][CH2:34][OH:35])=[C:26]([F:31])[CH:27]=4)[N:22]=3)=[N:19][N:20]=2)[CH:17]=1

Participants

4

Reactant 2

HCID 10756264(5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-nitrophenyl carbonateHCID 709845612-(2-(6-((R)-1-((S)-3-aminopyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoro quinolin-7-yloxy)ethanol

Product 1

HCID 70984291(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ((S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-(2-hydroxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-yl)carbamateYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 2-((2-(6-((R)-1-((S)-3-aminopyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoro quinolin-7-yl)oxy)ethanol (125 mg, 0.255 mmol) in DMF (1.5 mL) was added a solution of (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-nitrophenyl carbonate (prepared according to procedures described in J. Med. Chem. 1999, 42, 3994-4000, 71.2 mg, 0.255 mmol) in DMF (1 mL). The reaction mixture was stirred at ambient temperature for 30 minutes. The reaction was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with water and brine, dried and concentrated. The residue was purified by flash chromatography on silica gel (DCM:MeOH, 70:1 to 40:1) to give (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ((S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-(2-hydroxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-yl)carbamate (131 mg, 80%). LCMS APCI (+) m/z 647 (M+H).

Workup

  1. customThe reaction was partitioned between EtOAc and water
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washThe combined organic layers were washed with water and brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica gel (DCM:MeOH, 70:1 to 40:1)

Sources & evidence

ORD record
ord-22de57705a584fbd841505fed5a0520b
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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