Potassium Carbonate → HCID 86729246, compound

HRID 1399826Notes

Reaction equation

HRID 1399826 reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:30])[CH2:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:16]=1.Br[C:32]1[CH:33]=[N:34][C:35]2[C:40]([CH:41]=1)=[CH:39][CH:38]=[CH:37][CH:36]=2.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:30])[CH2:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:32]2[CH:33]=[N:34][C:35]3[C:40]([CH:41]=2)=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH:16]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 214133-BromoquinolineHCID 867292361-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)propan-2-ol

Product 1

HCID 86729246HCID 86729246, compoundYield 53.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)propan-2-ol (250 mg, 0.61 mmol) in Dioxane (3 mL) was added 3-bromoquinoline (127 mg, 0.61 mmol), 2N K2CO3 (1 mL, 2 mmol) and PdCl2(dppf)2 (20 mg, 0.025 mmol). The reaction mixture was heated at 120° C. under microwave conditions for 30 min. the mixture was then concentrated to remove the solvents, the residue dissolved in ethyl acetate and washed with water. The separated organic layer dried and concentrated to yield the crude product which was purified HPLC separation to give the title compound (133 mg, 53.2%). 1HNMR (CH3OD, 400 MHz) δ: 9.39 (s, 1H), 9.12-9.08 (m, 1H), 8.28-8.19 (m, 2H), 8.06-8.00 (m, 1H), 7.90-7.84 (m, 1H), 7.88-7.46 (m, 3H), 7.36-7.20 (m, 4H), 7.18-7.12 (m, 1H), 4.78-4.40 (m, 3H), 4.23-4.16 (m, 2H), 4.02-4.80 (m, 1H), 3.65-3.40 (m, 3H), 3.40-3.20 (m, 2H). LCMS (m/z): 411.2 [M+H]

Workup

  1. concentrationwas then concentrated
  2. customto remove the solvents
  3. dissolutionthe residue dissolved in ethyl acetate
  4. washwashed with water
  5. customThe separated organic layer dried
  6. concentrationconcentrated
  7. customto yield the crude product which
  8. customwas purified
  9. customHPLC separation

Sources & evidence

ORD record
ord-3874fd29cd4b4e809e477c217e39c542
Source dataset
uspto-grants-2014_12
Patent number
US08906900B2

Reaction notes

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