Cesium carbonate → (trans)-Naphthalen-2-ylmethyl 3-hydroxy-4-(2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)pyrrolidine-1-carboxylate

HRID 1095707Notes

Reaction equation

HRID 1095707 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].[CH3:7][O:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[CH:16][N:15]2[C:18]([C:21]3[CH:30]=[CH:29][C:28]4[C:23](=[C:24]([OH:31])[CH:25]=[CH:26][CH:27]=4)[N:22]=3)=[CH:19][N:20]=[C:14]2[CH:13]=1.[C@@H:32]12[O:37][C@@H:36]1[CH2:35][N:34]([C:38]([O:40][CH2:41][C:42]1[CH:51]=[CH:50][C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[CH:43]=1)=[O:39])[CH2:33]2>CN(C=O)C>[OH:37][C@H:32]1[C@H:36]([O:31][C:24]2[CH:25]=[CH:26][CH:27]=[C:28]3[C:23]=2[N:22]=[C:21]([C:18]2[N:15]4[CH:16]=[CH:17][C:12]([O:11][CH2:10][CH2:9][O:8][CH3:7])=[CH:13][C:14]4=[N:20][CH:19]=2)[CH:30]=[CH:29]3)[CH2:35][N:34]([C:38]([O:40][CH2:41][C:42]2[CH:51]=[CH:50][C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[CH:43]=2)=[O:39])[CH2:33]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 66781369HCID 66781369, compoundHCID 87149494(cis)-Naphthalen-2-ylmethyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate

Product 1

HCID 131729511(trans)-Naphthalen-2-ylmethyl 3-hydroxy-4-(2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Cs2CO3. (0.2201 g, 1.141 mmol) was added to a solution of 2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-ol (0.294 g, 0.878 mmol) and (cis)-naphthalen-2-ylmethyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate (0.260 g, 0.966 mmol) in DMF (4.5 mL). The reaction was heated to 100° C. overnight, then cooled and poured into 30 mL of ice water. This mixture was extracted with 25%. IP A in CH2Cl2, and the organic layer was dried over sodium sulfate and condensed. The residue was purified by silica gel chromatography, eluting with gradient from 1% to 25% MeOH (with 6% NH4OH) in EtOAc, to collect 223 mg of the desired product. MS APCI (+) m/z 605.1 (M+1) detected.

Workup

  1. temperaturecooled
  2. extractionThis mixture was extracted with 25%
  3. dry with materialIP A in CH2Cl2, and the organic layer was dried over sodium sulfate and condensed
  4. customThe residue was purified by silica gel chromatography
  5. washeluting with gradient from 1% to 25% MeOH (with 6% NH4OH) in EtOAc
  6. customto collect 223 mg of the desired product

Sources & evidence

ORD record
ord-d563e964638749cab5b06f00b6268f64
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

Loading…