Triphenylphosphine → (1S,4R)-4-(4,7-difluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enol

HRID 470171

反応式

HRID 470171 の反応式
[F:1][C:2]1[C:7]2[N:8]=[CH:9][NH:10][C:6]=2[C:5]([F:11])=[CH:4][N:3]=1.[H-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC([O:36][C@H:37]1[CH:41]=[CH:40][C@@H:39](O)[CH2:38]1)=O>CN(C=O)C.C1COCC1.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>[F:1][C:2]1[C:7]2[N:8]=[CH:9][N:10]([C@@H:40]3[CH2:41][C@H:37]([OH:36])[CH:38]=[CH:39]3)[C:6]=2[C:5]([F:11])=[CH:4][N:3]=1

参加物

9

反応物 4

HCID 11776TriphenylphosphineHCID 24758Sodium hydrideHCID 10154103rac-(1R,4S)-4-hydroxycyclopent-2-en-1-yl acetateHCID 178506010HCID 178506010、化合物

生成物 1

HCID 58329283(1S,4R)-4-(4,7-difluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enol

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

4,7-difluoro-1H-imidazo[4,5-c]pyridine (1-4) (2.0 g, 12.9 mmol, 1 equiv) was dissolved in dry DMF (21 mL). Sodium hydride (542 mg, 13.5 mmol, 1.05 equiv) was carefully added. The resulting mixture was stirred at ambient temperature for 45 minutes at which point triphenylphosphine (507 mg, 1.9 mmol, 0.15 equiv), Pd-tetrakis (745 mg, 0.6 mmol, 0.05 equiv) and (1R,3S)-(+)-cis-4-cyclopentene-1,3-diol 1-acetate (3-1) (2.2 g, 15.5 mmol, 1.2 equiv) in dry THF (21 mL) were added. The mixture was stirred at 60° C. for 16 hours, then cooled to ambient temperature, diluted with 100 mL EtOAc and washed with 50 mL water. The aqueous layer was washed with EtOAc three additional times, and the combined washings were dried over MgSO4, filtered and concentrated. The crude residue was purified by reverse phase chromatography (5-95% CH3CN/water with 0.1% TFA modifier) to afford (1S,4R)-4-(4,7-difluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enol (3-2) as a white solid. LRMS m/z (M+H) 238.0 found, 238.1 required.

後処理

  1. additionwere added
  2. temperaturecooled to ambient temperature
  3. washwashed with 50 mL water
  4. washThe aqueous layer was washed with EtOAc three additional times
  5. dry with materialthe combined washings were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by reverse phase chromatography (5-95% CH3CN/water with 0.1% TFA modifier)

出典と根拠

ORDレコード
ord-99a7170ad43d48d4bcf9588f4f702bd6
出典データセット
uspto-grants-2014_01
特許番号
US08629275B2

関連ノート

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