Cesium carbonate → HCID 131729516, compound

HRID 1095729Notes

Reaction equation

HRID 1095729 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][C@H:3]1[F:15].FC(F)(F)S(O[C:22]1[CH:23]=[CH:24][CH:25]=[C:26]2[C:31]=1[N:30]=[C:29]([C:32]1[N:36]3[CH:37]=[CH:38][C:39]([O:41][CH2:42][CH2:43][O:44][CH3:45])=[CH:40][C:35]3=[N:34][CH:33]=1)[CH:28]=[CH:27]2)(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[F:15][C@H:3]1[C@@H:2]([NH:1][C:22]2[CH:23]=[CH:24][CH:25]=[C:26]3[C:31]=2[N:30]=[C:29]([C:32]2[N:36]4[CH:37]=[CH:38][C:39]([O:41][CH2:42][CH2:43][O:44][CH3:45])=[CH:40][C:35]4=[N:34][CH:33]=2)[CH:28]=[CH:27]3)[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:9])[CH2:4]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 112644351,1-Dimethylethyl (3R,4S)-4-amino-3-fluoro-1-piperidinecarboxylateHCID 86642347HCID 86642347, compound

Product 1

HCID 131729516HCID 131729516, compoundYield 109.4%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

(cis)-tert-Butyl 4-amino-3-fluoropiperidine-1-carboxylate (0.040 g, 0.18 mmol) was combined with 2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yl trifluoromethanesulfonate (Steps 1A-1D; 0.065 g, 0.140 mmol), micronized Cs2CO3 (0.064 g, 0.197 mmol), BINAP-racemic (0.0087 g, 0.014 mmol) and Pd2dba3 (0.0064 g, 0.0070 mmol). The mixture was treated with toluene (0.75 mL), degassed with argon and heated to reflux for 16 hours. The reaction was cooled, diluted with CHCl3 and purified by silica gel chromatography, eluting with a gradient from 1-20% (6% NH4OH in MeOH)/ethyl acetate to provide the desired product (82 mg). MS ESI (+) m/z 536.1 (M+1) detected.

Workup

  1. customdegassed with argon
  2. temperatureheated
  3. temperatureto reflux for 16 hours
  4. temperatureThe reaction was cooled
  5. additiondiluted with CHCl3
  6. custompurified by silica gel chromatography
  7. washeluting with a gradient from 1-20% (6% NH4OH in MeOH)/ethyl acetate

Sources & evidence

ORD record
ord-2c0dcd0cfdd74f46a4e266c206809ccb
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

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