1,2-Dimethoxyethane → 9-tert-butyl-3-methoxy-2-pyridin-3-yl-15-(1,3-thiazol-5-yl)-5,6,9,10,11,12-hexahydro[1,5]oxazonino[8',7':4,5]pyrrolo[2,1-a]isoquinolin-8(14H)-one

HRID 1971664Notes

Reaction equation

HRID 1971664 reaction equation
Br[C:2]1[C:3]([O:32][CH3:33])=[CH:4][C:5]2[CH2:6][CH2:7][N:8]3[C:14]4[C:15](=[O:26])[N:16]([C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:17][CH2:18][CH2:19][O:20][CH2:21][C:13]=4[C:12]([C:27]4[S:31][CH:30]=[N:29][CH:28]=4)=[C:9]3[C:10]=2[CH:11]=1.[N:34]1[CH:39]=[CH:38][CH:37]=[C:36](B(O)O)[CH:35]=1.C([O-])([O-])=O.[K+].[K+].C(COC)OC>O>[C:22]([N:16]1[C:15](=[O:26])[C:14]2[N:8]3[CH2:7][CH2:6][C:5]4[CH:4]=[C:3]([O:32][CH3:33])[C:2]([C:36]5[CH:35]=[N:34][CH:39]=[CH:38][CH:37]=5)=[CH:11][C:10]=4[C:9]3=[C:12]([C:27]3[S:31][CH:30]=[N:29][CH:28]=3)[C:13]=2[CH2:21][O:20][CH2:19][CH2:18][CH2:17]1)([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 58124867HCID 58124867, compound

Product 1

HCID 581249459-tert-butyl-3-methoxy-2-pyridin-3-yl-15-(1,3-thiazol-5-yl)-5,6,9,10,11,12-hexahydro[1,5]oxazonino[8',7':4,5]pyrrolo[2,1-a]isoquinolin-8(14H)-oneYield 93.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 75 mg of 8e, 35 mg of pyridine-3-boronic acid, 60 mg of K2CO3 in 2 ml of degassed 90% aq. dimethoxyethane was heated at 90° C. for 16 h The reaction mixture was cooled, diluted with water and extracted with ethyl acetate. The organic layer was once washed with 1M K2CO3, once with water, dried and concentrated. The crude material was chromatographed over silica gel using a gradient of toluene/acetone. The isolated material was treated with diethyl ether and provided 70 mg of 8f; Mp 200-201° C.; Rf 0.15 (toluene/acetone 7/3). MS-ESI: [M+1] 529.3.

Workup

  1. temperaturewas cooled
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was once washed with 1M K2CO3, once with water
  4. customdried
  5. concentrationconcentrated
  6. customThe crude material was chromatographed over silica gel using a gradient of toluene/acetone
  7. additionThe isolated material was treated with diethyl ether

Sources & evidence

ORD record
ord-5d7fe8e09b744cf08f2ea8ed1f05612e
Source dataset
uspto-grants-2013_04
Patent number
US08431564B2

Reaction notes

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