Diisopropylethylamine → (4-{5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid

HRID 241166Notes

Reaction equation

HRID 241166 reaction equation
Cl.[O:2]1[C:8]2[CH:9]=[CH:10][C:11]([B:13]([OH:15])[OH:14])=[CH:12][C:7]=2[CH2:6][NH:5][CH2:4][CH2:3]1.Cl[C:17]1[C:22]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)=[C:21]([CH3:31])[N:20]=[CH:19][N:18]=1.C(N(C(C)C)CC)(C)C>>[F:30][C:27]1[CH:26]=[CH:25][C:24]([CH2:23][C:22]2[C:17]([N:5]3[CH2:6][C:7]4[CH:12]=[C:11]([B:13]([OH:15])[OH:14])[CH:10]=[CH:9][C:8]=4[O:2][CH2:3][CH2:4]3)=[N:18][CH:19]=[N:20][C:21]=2[CH3:31])=[CH:29][CH:28]=1

Participants

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 66820605(2,3,4,5-Tetrahydrobenzo[f][1,4]oxazepin-7-yl)boronic acid hydrochlorideHCID 866478404-Chloro-5-(4-fluorobenzyl)-6-methylpyrimidine

Product 1

HCID 66820119(4-{5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acidYield 35.2%

Conditions

Temperature
95 °C

Procedure

A mixture of 2,3,4,5-tetrahydro-1,4-benzoxazepin-7-ylboronic acid hydrochloride salt (1.20 g, 5.2 mmol), 4-chloro-5-(4-fluorobenzyl)-6-methylpyrimidine (reagent preparation 5) (1.24 g, 5.2 mmol), diisopropylethylamine (0.40 mL, 2.10 mmol) 50% aqueous 1,4-dioxane (50 mL) was deoxygenated for five minutes by bubbling nitrogen gas then stirred at 95° C. for 18 hours. The reaction mixture was concentrated, diluted with water (50 mL), adjusted to pH 14, and then washed with isopropyl acetate (3×30 mL). The aqueous mixture was adjusted to pH 8 and the white solid precipitated was collected by filtration, washed with water and dried to give (4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid (0.72 g, 35% yield). MS (EI) for C2H21BFN3O3: 394 (MH+).

Workup

  1. customwas deoxygenated for five minutes
  2. customby bubbling nitrogen gas
  3. concentrationThe reaction mixture was concentrated
  4. additiondiluted with water (50 mL)
  5. washwashed with isopropyl acetate (3×30 mL)
  6. customthe white solid precipitated
  7. filtrationwas collected by filtration
  8. washwashed with water
  9. customdried

Sources & evidence

ORD record
ord-778d3f430e9f4e09bfeb8a99b85e1379
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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