Diisopropylethylamine → 4-(5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine

HRID 241191Notes

Reaction equation

HRID 241191 reaction equation
Cl.[CH3:2][C:3]1([CH3:21])[C:7]([CH3:9])([CH3:8])[O:6][B:5]([C:10]2[CH:11]=[CH:12][C:13]3[O:19][CH2:18][CH2:17][NH:16][CH2:15][C:14]=3[CH:20]=2)[O:4]1.CCN(C(C)C)C(C)C.Cl[C:32]1[C:37]([CH2:38][C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=2)=[C:36]([CH3:46])[N:35]=[CH:34][N:33]=1>CN1C(=O)CCC1>[F:45][C:42]1[CH:41]=[CH:40][C:39]([CH2:38][C:37]2[C:32]([N:16]3[CH2:15][C:14]4[CH:20]=[C:10]([B:5]5[O:4][C:3]([CH3:21])([CH3:2])[C:7]([CH3:8])([CH3:9])[O:6]5)[CH:11]=[CH:12][C:13]=4[O:19][CH2:18][CH2:17]3)=[N:33][CH:34]=[N:35][C:36]=2[CH3:46])=[CH:44][CH:43]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 668206297-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine hydrochlorideHCID 866478404-Chloro-5-(4-fluorobenzyl)-6-methylpyrimidine

Product 1

HCID 668205164-(5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepineYield 79.5%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine hydrochloride (1.4 g, 4.5 mmol) and DIPEA (6.4 mL, 37 mmol) in NMP (24 mL) was added and 4-chloro-5-(4-fluorobenzyl)-6-methylpyrimidine (reagent preparation 5) (1.7 g, 7.3 mmol). The resulting mixture was heated (120° C.) for 12 h and then partitioned between ethyl acetate (100 mL) and 1N aqueous hydrochloric acid (50 mL). The organic layer was washed with additional 1N aqueous hydrochloric acid (50 mL), brine (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated. Column chromatography on silica (0-30% ethyl acetate/hexanes) provided 4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine (1.7 g, 47% yield) as a white foam. MS (EI) for C27H31BFN3O3: 476 (MH+).

Workup

  1. custompartitioned between ethyl acetate (100 mL) and 1N aqueous hydrochloric acid (50 mL)
  2. washThe organic layer was washed with additional 1N aqueous hydrochloric acid (50 mL), brine (50 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-f958011dc0a54628b1a6f1fdec9bd212
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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