Water → HCID 66747718, compound

HRID 2401883Notes

Reaction equation

HRID 2401883 reaction equation
Br[CH2:2][C:3]1[C:7]([C:8]#[N:9])=[C:6]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[S:5][C:4]=1[C:16]([O:18][CH3:19])=[O:17].[CH:20]1[C:29]2[C:24](=[CH:25][CH:26]=[C:27](B(O)O)[CH:28]=2)[CH:23]=[CH:22][N:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1.O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:8]([C:7]1[C:3]([CH2:2][C:27]2[CH:28]=[C:29]3[C:24]([CH:23]=[CH:22][N:21]=[CH:20]3)=[CH:25][CH:26]=2)=[C:4]([C:16]([O:18][CH3:19])=[O:17])[S:5][C:6]=1[N:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)#[N:9]

Participants

7

Reactant 5

HCID 962WaterHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 23597419Isoquinolin-7-ylboronic acidHCID 66748038HCID 66748038, compound

Product 1

HCID 66747718HCID 66747718, compoundYield 70.6%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

A mixture of methyl 3-(bromomethyl)-4-cyano-5-(morpholin-4-yl)thiophene-2-carboxylate (0.128 g, 0.371 mmol), isoquinoline-7-boronic acid (101 mg, 0.584 mmol), tetrakis(triphenylphosphine)palladium(0) (21.4 mg, 0.0185 mmol) and cesium carbonate (0.242 g, 0.742 mmol) was suspended in 1,4-dioxane (8.0 mL, 100 mmol) and Water (0.60 mL, 33 mmol) under N2 atmosphere in a 20 mL vial. The vial was capped and heated to 90° C. for 1 hour. The mixture was cooled to room temperature and concentrated in vacuum. The residue was suspended in DCM and filtered over a celite pad. The filtrate was chromatographed in a silica gel column using MeOH/DCM (0/100 to 3/97) to afford a solid product (103 mg, 66.4%). LC/MS: (FA) ES+ 394. 1H NMR (400 MHz, d-chloroform) δ 9.20 (s, 1H), 8.47 (d, J=5.77 Hz, 1H), 7.87 (s, 1H), 7.73 (d, J=5.77 Hz, 1H), 7.60 (d, J=5.77 Hz, 1H), 7.44-7.48 (m, 1H), 4.60 (s, 2H), 3.86 (s, 3H), 3.84 (m, 4H), 3.59 (m, 4H).

Workup

  1. customThe vial was capped
  2. temperatureThe mixture was cooled to room temperature
  3. concentrationconcentrated in vacuum
  4. filtrationfiltered over a celite pad
  5. customThe filtrate was chromatographed in a silica gel column

Sources & evidence

ORD record
ord-f5a1aa1ab88747c99996b9b7568f4fb9
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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