Dichloromethane → N-[5-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl]benzamide

HRID 241167Notes

Reaction equation

HRID 241167 reaction equation
Br[C:2]1[N:7]=[C:6]2[S:8][C:9]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[N:10][C:5]2=[CH:4][CH:3]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][C:28]2[C:29]([N:35]3[CH2:41][C:40]4[CH:42]=[C:43](B(O)O)[CH:44]=[CH:45][C:39]=4[O:38][CH2:37][CH2:36]3)=[N:30][CH:31]=[N:32][C:33]=2[CH3:34])=[CH:23][CH:22]=1.C(N(C(C)C)CC)(C)C.ClCCl>CN(C)C=O.C(OCC)(=O)C>[F:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][C:28]2[C:29]([N:35]3[CH2:41][C:40]4[CH:42]=[C:43]([C:2]5[N:7]=[C:6]6[S:8][C:9]([NH:11][C:12](=[O:19])[C:13]7[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=7)=[N:10][C:5]6=[CH:4][CH:3]=5)[CH:44]=[CH:45][C:39]=4[O:38][CH2:37][CH2:36]3)=[N:30][CH:31]=[N:32][C:33]=2[CH3:34])=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 457894382-Benzamido-5-bromo-[1,3]thiazolo[5,4-b]pyridineHCID 66820119(4-{5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid

Product 1

HCID 86647850N-[5-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl]benzamideYield 41%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
105 °C

Procedure

A solution of N-(5-bromothiazolo[5,4-b]pyridin-2-yl)benzamide (reagent preparation 13) (0.14 g, 0.42 mmol), (4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid (0.14 g, 0.35 mmol) and diisopropyethylamine (0.40 mL, 2.10 mmol) in 10% aqueous dimethylformamide (3 mL) was deoxygenated for five minutes by bubbling nitrogen gas, followed by the addition of 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) complex with dichloromethane (20 mg, 0.021 mmol). The reaction mixture was heated to 105° C. for 4 hours. On cooling to room temperature the mixture was diluted with ethyl acetate (50 mL) then it was filtered through a pad of Celite. The organic filtrate was washed with 10% aqueous citric acid (20 mL), brine, aqueous saturated sodium bicarbonate (20 mL) and brine then dried over anhydrous sodium sulfate, filtered and concentrated. Silica gel chromatography (chloroform/methanol 95:5 to 9:1) provided N-[5-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl]benzamide (86 mg. 41%). MS (EI) for C34H27FN6O2S: 603 (MH+).

Workup

  1. customby bubbling nitrogen gas
  2. temperatureOn cooling to room temperature the mixture
  3. filtrationit was filtered through a pad of Celite
  4. washThe organic filtrate was washed with 10% aqueous citric acid (20 mL), brine, aqueous saturated sodium bicarbonate (20 mL) and brine
  5. dry with materialthen dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-e41f79a307bb4c869b16eec9244be819
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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