Cesium carbonate → tert-butyl 4-(4-(3-cyclopropyl-4-((R)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyridin-6-yl)-2-methoxyphenyl)piperazine-1-carboxylate

HRID 2209252Notes

Reaction equation

HRID 2209252 reaction equation
Cl[C:2]1[CH:3]=[C:4]([O:14][C@@H:15]([C@H:17]2[CH2:21][N:20]([C@@H:22]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=3)[CH3:23])[C:19](=[O:32])[CH2:18]2)[CH3:16])[C:5]2[N:6]([N:8]=[CH:9][C:10]=2[CH:11]2[CH2:13][CH2:12]2)[CH:7]=1.[CH3:33][O:34][C:35]1[CH:40]=[C:39](B2OC(C)(C)C(C)(C)O2)[CH:38]=[CH:37][C:36]=1[N:50]1[CH2:55][CH2:54][N:53]([C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[CH2:52][CH2:51]1.C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.O.CCOC(C)=O>[CH:11]1([C:10]2[CH:9]=[N:8][N:6]3[CH:7]=[C:2]([C:39]4[CH:38]=[CH:37][C:36]([N:50]5[CH2:55][CH2:54][N:53]([C:56]([O:58][C:59]([CH3:60])([CH3:61])[CH3:62])=[O:57])[CH2:52][CH2:51]5)=[C:35]([O:34][CH3:33])[CH:40]=4)[CH:3]=[C:4]([O:14][C@@H:15]([C@@H:17]4[CH2:18][C:19](=[O:32])[N:20]([C@@H:22]([C:24]5[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=5)[CH3:23])[CH2:21]4)[CH3:16])[C:5]=23)[CH2:12][CH2:13]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 89494488Tert-butyl 4-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylate2×HCID 117842976(R)-4-((R)-1-((6-chloro-3-cyclopropylpyrazolo[1,5-a]pyridin-4-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Product 1

HCID 117843525tert-butyl 4-(4-(3-cyclopropyl-4-((R)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyridin-6-yl)-2-methoxyphenyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

(R)-4-((R)-1-((6-chloro-3-cyclopropylpyrazolo[1,5-a]pyridin-4-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one (32 mg, 0.070 mmol), tert-butyl 4-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylate Intermediate 7.08 (44 mg, 0.11 mmol) and Cs2CO3 (69 mg, 0.21 mmol) were dissolved in 1,2-dimethoxyethane (6.0 mL) and water (3.0 mL). The mixture was degassed with nitrogen for 5 minutes and PEPPSI-IPr catalyst (4.8 mg, 0.0071 mmol) was added. The mixture was heated for 10 minutes at 95° C., cooled and diluted with EtOAc and water. The layers were separated and organics were dried (MgSO4), filtered and concentrated to provide tert-butyl 4-(4-(3-cyclopropyl-4-((R)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyridin-6-yl)-2-methoxyphenyl)piperazine-1-carboxylate which was used directly in the next reaction. LCMS-ESI+ (m/z): [M+H]+ calcd for C41H51N5O6: 710.4; found: 710.3.

Workup

  1. customThe mixture was degassed with nitrogen for 5 minutes
  2. temperaturecooled
  3. customThe layers were separated
  4. dry with materialorganics were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-2176e4fa89b44e399237080093b3371f
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

Loading…