Potassium Carbonate → benzyl 2,4-bis(benzyloxy)-6-(2-((tert-butoxycarbonyl)amino)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-7-yl)-5-methylnicotinate

HRID 1481792Notes

Reaction equation

HRID 1481792 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:17]=[CH:16][C:15]3[N:14]4[CH2:18][CH:19]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][C:13]4=[CH:12][C:11]=3[CH:10]=2)O1.[CH2:30]([O:37][C:38]1[N:53]=[C:52](Cl)[C:51]([CH2:55]C)=[C:50]([O:57][CH2:58][C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[C:39]=1[C:40]([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:41])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(=O)([O-])[O-].[K+].[K+].F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>CS(C)=O.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[CH2:30]([O:37][C:38]1[N:53]=[C:52]([C:9]2[CH:17]=[CH:16][C:15]3[N:14]4[CH2:18][CH:19]([NH:21][C:22]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:28])[CH2:20][C:13]4=[CH:12][C:11]=3[CH:10]=2)[C:51]([CH3:55])=[C:50]([O:57][CH2:58][C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[C:39]=1[C:40]([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:41])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 44558591Tri-t-butylphosphine fluoroborateHCID 86280413Benzyl 2,4-bis(benzyloxy)-6-chloro-5-ethylnicotinateHCID 123500811tert-butyl (7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-2-yl)carbamate

Product 1

HCID 71284342benzyl 2,4-bis(benzyloxy)-6-(2-((tert-butoxycarbonyl)amino)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-7-yl)-5-methylnicotinateYield 55.1%

Reagents, catalysts & solvents 2

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

The intermediate from Step 2 (280 mg, 0.7 mmol) was combined with benzyl 2,4-bis(benzyloxy)-6-chloro-5-methylnicotinate (332 mg, 0.7 mmol, prepared according to Example 379, Step 3), potassium carbonate (193 mg, 1.4 mmol), tris(dibenzylideneacetone) dipalladium(0) (32 mg, 0.035 mmol) and tri-tert-butylphosphine tetrafluoroborate (41 mg, 0.14 mmol) in DMSO (3 mL). The mixture was heated under Ar at 120° C. for 20 min. The mixture was cooled to room temperature and partitioned in CH2Cl2 (10 mL) and saturated aqueous NaHCO3 (10 mL). The organic layer was removed, concentrated and chromatographed on silica gel (0-30% EtOAc in hexanes) to provide the product as a white powder (274 mg, 55%).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned in CH2Cl2 (10 mL)
  3. customThe organic layer was removed
  4. concentrationconcentrated
  5. customchromatographed on silica gel (0-30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-11ac0a5b038c4268836630ce05dbdad4
Source dataset
uspto-grants-2016_08
Patent number
US09409905B2

Reaction notes

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