Water → HCID 86639683, compound

HRID 1426134Notes

Reaction equation

HRID 1426134 reaction equation
[ClH:1].[CH2:2]([O:9][C:10]1[C:11]([NH:17][C:18]2[S:19][CH:20]=[C:21]([CH3:23])[N:22]=2)=[N:12][CH:13]=[C:14](Br)[CH:15]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:24](B1C2CCCC1CCC2)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.O>CN(C=O)C.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].ClCCl>[ClH:1].[CH2:24]([C:14]1[CH:15]=[C:10]([O:9][CH2:2][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[C:11]([NH:17][C:18]2[S:19][CH:20]=[C:21]([CH3:23])[N:22]=2)=[N:12][CH:13]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 3

HCID 962WaterHCID 41509249-Benzyl-9-borabicyclo(3.3.1)nonaneHCID 160614653-(benzyloxy)-5-bromo-N-(4-methylthiazol-2-yl)pyridin-2-amine hydrochloride

Product 1

HCID 86639683HCID 86639683, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

3-(Benzyloxy)-5-bromo-N-(4-methylthiazol-2-yl)pyridin-2-amine (prepared according to Example 1) (0.125 g, 0.332 mmol), 9-benzyl-9-bora-bicyclo[3.3.1]nonane (1.99 mL, 0.997 mmol), PdCl2(dppf) dichloromethane adduct (0.0273 g, 0.0332 mmol), were placed in DMF (6 mL), and water (0.6 mL) and heated to 60° C. for 18 hours. The reaction mixture was cooled and partitioned between water and DCM. The layers were separated and the organic layer was dried, filtered, and concentrated. Crude material was purified by silica gel to give the free base of the title compound (92%). The free base was purified by reverse phase chromatography. The purified free base was dissolved in DCM and 2M HCl was added. The mixture was concentrated to give 5-benzyl-3-(benzyloxy)-N-(4-methylthiazol-2-yl)pyridin-2-amine (0.038 g, 29.5% yield). 1H NMR (DMSO-d6) δ 7.88 (s, 1H), 7.57 (m, 3H), 7.38 (m, 3H), 7.27 (m, 4H), 7.21 (m, 1H), 6.83 (s, 1H), 5.29 (s, 2H), 3.94 (s, 2H), 2.31 (s, 3H). Mass spectrum (apci) m/z=388.1 (M+H-HCl).

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between water and DCM
  3. customThe layers were separated
  4. customthe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customCrude material was purified by silica gel

Sources & evidence

ORD record
ord-d884a26dec8d44f5aea3422fef325e17
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

Loading…