Potassium Carbonate → 1,1-dimethylethyl (2S)-4-{[5'-(aminomethyl)-2'-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate

HRID 2080330ノート

反応式

HRID 2080330 の反応式
Cl.Br[C:3]1[CH:4]=[C:5]([CH2:10][NH2:11])[CH:6]=[CH:7][C:8]=1[F:9].[CH3:12][C:13]([O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]2[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=2)[CH2:21][C@@H:20]1[CH3:35])=[O:18])([CH3:15])[CH3:14].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:11][CH2:10][C:5]1[CH:6]=[CH:7][C:8]([F:9])=[C:3]([C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([CH2:25][N:22]3[CH2:23][CH2:24][N:19]([C:17]([O:16][C:13]([CH3:15])([CH3:14])[CH3:12])=[O:18])[C@@H:20]([CH3:35])[CH2:21]3)[CH:27]=2)[CH:4]=1

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 27249011-(3-Bromo-4-fluorophenyl)methanamine hydrochlorideHCID 25132855{3-[((3S)-4-{[(1,1-dimethylethyl)oxy]carbonyl}-3-methyl-1-piperazinyl)methyl]phenyl}boronic acid

生成物 1

HCID 251325161,1-dimethylethyl (2S)-4-{[5'-(aminomethyl)-2'-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate収率 37.3%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 8857Ethyl Acetate溶媒HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
150 °C

実験手順

To a solution of [(3-bromo-4-fluorophenyl)methyl]amine hydrochloride (1.68 g, 7 mmol) in dioxane/H2O (10 mL/3.3 mL) was added {3-[((3S)-4-{[(1,1-dimethylethyl)oxy]carbonyl}-3-methyl-1-piperazinyl)methyl]phenyl}boronic acid (2.33 g, 7 mmol), K2CO3 (4.83, 35 mmol) and Pd(PPh3)4 (405 mg, 0.35 mmol). The resulting mixture was heated at 150° C. in a pressure vessel for 2 hours, then cooled to rt and diluted with EtOAc (50 mL). The organic layer was collected and the aqueous layer was extracted by EtOAc (30 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The residue was purified by Gilson preparatory HPLC, eluting with acetonitrile/water/0.1% TFA (10/90 to 90/10, v/v, over 12 min), to give the title compound (1.08 g, 37%). LC/MS: m/z, 414 (M+H), 1.83 min.

後処理

  1. temperaturecooled to rt
  2. customThe organic layer was collected
  3. extractionthe aqueous layer was extracted by EtOAc (30 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by Gilson preparatory HPLC
  8. washeluting with acetonitrile/water/0.1% TFA (10/90 to 90/10

出典と根拠

ORDレコード
ord-0ca4abd654c54d1ab340093a7dd43ca1
出典データセット
uspto-grants-2011_04
特許番号
US07932247B2

反応ノート

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