Water → (3R,4R)-naphthalen-2-ylmethyl 3-fluoro-4-(6-fluoro-2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)piperidine-1-carboxylate

HRID 1095759Notes

Reaction equation

HRID 1095759 reaction equation
[F:1][C@H:2]1[C@@H:7]([O:8]S(C)(=O)=O)[CH2:6][CH2:5][N:4]([C:13]([O:15][CH2:16][C:17]2[CH:26]=[CH:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:18]=2)=[O:14])[CH2:3]1.[F:27][C:28]1[CH:29]=[C:30]2[C:35](=[C:36](O)[CH:37]=1)[N:34]=[C:33]([C:39]1[N:43]3[CH:44]=[CH:45][C:46]([O:48][CH2:49][CH2:50][O:51][CH3:52])=[CH:47][C:42]3=[N:41][CH:40]=1)[CH:32]=[CH:31]2.C([O-])([O-])=O.[Cs+].[Cs+].O>CC(N(C)C)=O.CCOC(C)=O>[F:1][C@H:2]1[C@H:7]([O:8][C:36]2[CH:37]=[C:28]([F:27])[CH:29]=[C:30]3[C:35]=2[N:34]=[C:33]([C:39]2[N:43]4[CH:44]=[CH:45][C:46]([O:48][CH2:49][CH2:50][O:51][CH3:52])=[CH:47][C:42]4=[N:41][CH:40]=2)[CH:32]=[CH:31]3)[CH2:6][CH2:5][N:4]([C:13]([O:15][CH2:16][C:17]2[CH:26]=[CH:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:18]=2)=[O:14])[CH2:3]1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 583692626-Fluoro-2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-olHCID 86638611(3R,4S)-naphthalen-2-ylmethyl 3-fluoro-4-(methylsulfonyloxy)piperidine-1-carboxylate

Product 1

HCID 66782069(3R,4R)-naphthalen-2-ylmethyl 3-fluoro-4-(6-fluoro-2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)piperidine-1-carboxylateYield 97.7%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

(3R,4S)-naphthalen-2-ylmethyl 3-fluoro-4-(methylsulfonyloxy)piperidine-1-carboxylate (170 mg, 0.44 mmol) (Example 20, Step F, derived from Peak 2), 6-fluoro-2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-ol (173 mg, 0.49 mmol) and Cs2CO3 (290 mg, 0.89 mmol) were weighed into a flask and suspended in 10 mL of DMA. The reaction was then heated to 90° C. overnight. The reaction was then cooled to ambient temperature, followed by workup with water and EtOAc. The combined organic phase was concentrated in vacuo, followed by flash column chromatography (1-10% MeOH/DCM) affording the desired product as a brown semi-solid (270 mg, 0.43 mmol, 95%). MS APCI (+) m/z 639.2 and 640.1 (M+1/+3) detected.

Workup

  1. temperatureThe reaction was then cooled to ambient temperature
  2. concentrationThe combined organic phase was concentrated in vacuo

Sources & evidence

ORD record
ord-6496fed86a144b03b07d08eb96adc5ab
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

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