Acetic Acid → HCID 178452458、化合物

HRID 2075772

反応式

HRID 2075772 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[C:11]([C:15]3[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:16]=3[OH:22])=[N:12][NH:13][CH:14]=2)=[CH:4][CH:3]=1.[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][O:33][CH2:32][C@H:31]1[C:36](O)=[O:37])=[O:29])([CH3:26])([CH3:25])[CH3:24].C(N=C=NC(C)C)(C)C.O[Li].O.C(O)(=O)C>ClCCl.O.C(OCC)(=O)C>[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][O:33][CH2:32][C@H:31]1[C:36](=[O:37])[NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[C:11]([C:15]3[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:16]=3[OH:22])=[N:12][NH:13][CH:14]=2)=[CH:4][CH:3]=1)=[O:29])([CH3:26])([CH3:25])[CH3:24]

参加物

9

反応物 5

HCID 176Acetic AcidHCID 12734DiisopropylcarbodiimideHCID 168937Lithium hydroxide, monohydrateHCID 1512537(3S)-4-(tert-Butoxycarbonyl)morpholine-3-carboxylic acidHCID 1785075482-[4-(4-Amino-phenylethynyl)-1H-pyrazol-3-yl]-4-chloro-phenol

生成物 1

HCID 178452458HCID 178452458、化合物収率 71.4%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of compound 24A (930 mg, 3.0 mmol) and (S)-morpholine-3,4-dicarboxylic acid 4-tert-butyl ester (19A, 2.09 g, 9.0 mmol) in anhydrous dichloromethane (20 mL) was added N,N′-diisopropylcarbodiimide (DIPC, 1.4 mL, 9.0 mmol). The reaction mixture was stirred at rt overnight. Solvent was removed. To the residua were added THF (20 mL) and methanol (20 mL) and a solution of LiOH.H2O (1.0 g, 23.84 mmol) in water (10 mL). The mixture was stirred at rt for 2 h. It was then neutralized with acetic acid (1.36 mL, 23.84 mmol). The mixture was diluted with ethyl acetate (˜100 mL), washed with brine, and dried over sodium sulfate. It was filtered, concentrated and filtered again to remove diisopropylurea. The filtrate was purified with silica column chromatography eluting with dichloromethane/ethyl acetate (v/v 5/1, 3/1, 2/1, 1/1) to provide the title compound (28A, 1.12 g) as a yellowish solid in 71.3% yield. LCMS (ESI) m/z 587.15 (MNa+), 521.05 (MH+), 421.06; HPLC: tR=5.32 min.

後処理

  1. customSolvent was removed
  2. additionTo the residua were added THF (20 mL) and methanol (20 mL)
  3. stirringThe mixture was stirred at rt for 2 h
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationIt was filtered
  7. concentrationconcentrated
  8. filtrationfiltered again
  9. customto remove diisopropylurea
  10. customThe filtrate was purified with silica column chromatography
  11. washeluting with dichloromethane/ethyl acetate (v/v 5/1, 3/1, 2/1, 1/1)

出典と根拠

ORDレコード
ord-adbb3e7842b04fda9aaad5fd9a282c7c
出典データセット
uspto-grants-2011_04
特許番号
US07923004B2

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