Toluene → HCID 67348445, compound

HRID 1676269Notes

Reaction equation

HRID 1676269 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[F:7][C:8]1[CH:9]=[C:10]([CH:12]=[CH:13][C:14]=1[O:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]2[CH:22]=[C:23](I)[S:24][C:17]=12)[NH2:11].[C:26]1(B(O)O)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C1(C)C=CC=CC=1>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.CCO>[F:7][C:8]1[CH:9]=[C:10]([NH2:11])[CH:12]=[CH:13][C:14]=1[O:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]2[CH:22]=[C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[S:24][C:17]=12

Participants

8

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 584749503-Fluoro-4-((2-iodothieno[3,2-b]pyridin-7-yl)oxy)aniline

Product 1

HCID 67348445HCID 67348445, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A vigorously stirred mixture of cesium carbonate (190 mg, 0.583 mmol), 3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)benzenamine (Example 6, Step A; 150 mg, 0.388 mmol), phenylboronic acid (59.2 mg, 0.486 mmol), toluene (4 mL) and EtOH (1 mL) was degassed under nitrogen for 10 minutes, and then Pd(PPh3)4 (22.4 mg, 0.0194 mmol) was added. The reaction mixture was heated at 80° C. for 18 hours, then cooled to room temperature and diluted with water (20 mL). The reaction mixture was extracted with EtOAc, and the organic layer was dried organic over sodium sulfate, filtered and concentrated. The residue was purified on a Biotage 40S (2:1 EtOAc/Hexane). The product was a light orange solid (75 mg, 53%). 1H NMR (CDCl3, 400 MHz) δ 8.46 (d, J=5.5 Hz, 1H), 7.75 (m, 3H), 7.46 (t, J=7.2 Hz, 2H), 7.40 (m, 1H), 7.06 (t, J=8.8 Hz, 1H), 6.54 (m, 1H), 6.50 (m, 2H), 3.84 (br s, 2H). LRMS (ESI pos) m/e 337 (M+1).

Workup

  1. customwas degassed under nitrogen for 10 minutes
  2. temperaturecooled to room temperature
  3. extractionThe reaction mixture was extracted with EtOAc
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified on a Biotage 40S (2:1 EtOAc/Hexane)

Sources & evidence

ORD record
ord-b77b3291b6fe41f0bba3f2f77be17d6a
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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