1,4-Dioxane → HCID 178474392, compound

HRID 473897Notes

Reaction equation

HRID 473897 reaction equation
[F:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([N:11]2[CH2:17][C:16]3[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][C:15]=3[O:14][CH2:13][CH2:12]2)=[O:10])[CH2:5][CH2:4]1.Br[C:26]1[CH:27]=[CH:28][C:29]2[N:33]=[C:32]([NH:34][C:35](=[O:37])[CH3:36])[NH:31][C:30]=2[CH:38]=1.O1CCOCC1.CCN(C(C)C)C(C)C>C(OCC)(=O)C.O>[F:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([N:11]2[CH2:17][C:16]3[CH:18]=[C:19]([C:26]4[CH:27]=[CH:28][C:29]5[NH:33][C:32]([NH:34][C:35](=[O:37])[CH3:36])=[N:31][C:30]=5[CH:38]=4)[CH:20]=[CH:21][C:15]=3[O:14][CH2:13][CH2:12]2)=[O:10])[CH2:5][CH2:4]1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 11054189N-(6-bromo-1H-benzimidazol-2-yl)acetamideHCID 67514561(4-{[4-(Fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid

Product 1

HCID 178474392HCID 178474392, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

(4-{[4-(fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid (67.2 mg, 0.2 mmol), N-(6-bromo-1H-benzimidazol-2-yl)acetamide (34.8 mg, 0.14 mmol) and dichloro[1,1-bis(diphenylphosphino]ferrocenepalladium (II) dichloromethane adduct (6 mg) was taken into dioxane (0.5 mL) followed by addition of water (0.1 mL) and DIPEA (0.14 mL). The resulting mixture was heated in a sealable vessel at 85° C. for 12 h then cooled to room temperature. The mixture was diluted with ethyl acetate, dried over anhydrous sodium sulfate and filtered through a silica plug with an ethyl acetate wash. The organic filtrate was washed once with 1M aqueous sodium hydroxide, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was chromatographed on silica gel (100% ethyl acetate to 4:1 ethyl acetate:ethanol) to give N-[5-(4-{[4-(fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazol-2-yl]acetamide as a colorless solid. 1H NMR (400 MHz, d4-methanol): 7.64 (dd, 1H), 7.51-7.48 (m, 2H), 7.46 (dd, 1H), 7.40 (dd, 1H), 7.03 (d, 1H), 4.49 (s, 2H), 4.35 (d, 1H), 4.23 (d, 1H), 4.19 (m, 2H), 3.74 (d, 2H), 3.68 (m, 2H), 2.85 (br tr, 2H), 2.25 (s, 3H), 1.88 (br, 1H), 1.71 (d, 2H), 1.36 (d q, 2H). MS (EI) for C25H28FN5O3: 337 (MH+).

Workup

  1. temperaturethen cooled to room temperature
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered through a silica plug with an ethyl acetate
  4. washwash
  5. washThe organic filtrate was washed once with 1M aqueous sodium hydroxide
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed on silica gel (100% ethyl acetate to 4:1 ethyl acetate:ethanol)

Sources & evidence

ORD record
ord-3ffe4a196a524ca1837cfe234bd42c36
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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