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Formic Acid → HCID 59255293、化合物

HRID 1891580
ノート
印刷プレビュー

反応式

HRID 1891580 の反応式
Cl[C:2]1[CH:3]=[C:4]([C:9]2[CH:13]=[C:12]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)=[CH:17][CH:16]=3)[O:11][N:10]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.C(O)=O.C(N(CC)C(C)C)(C)C.O>CN1CCCC1=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.C(OCC)(=O)C>[N:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[O:22][CH2:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][C:12]2[O:11][N:10]=[C:9]([C:4]3[C:5]([NH2:8])=[N:6][CH:7]=[CH:2][CH:3]=3)[CH:13]=2)=[CH:16][CH:17]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 284Formic AcidHCID 962WaterHCID 81531DiisopropylethylamineHCID 592552525-Chloro-3-(5-(4-(pyridin-2-yloxymethyl)-benzyl)-isoxazol-3-yl)-pyridin-2-ylamine

生成物 1

HCID 59255293HCID 59255293、化合物収率 2%

試薬・触媒・溶媒 3

HCID 178418397
HCID 178418397、化合物
触媒
HCID 8857Ethyl Acetate溶媒
HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
100 °C

実験手順

To a solution of 5-chloro-3-(5-(4-(pyridin-2-yloxymethyl)-benzyl)-isoxazol-3-yl)-pyridin-2-ylamine (37 mg, 94 μmol) described in Manufacturing Example 30-1-3 in N-methyl-2-pyrrolidinone (2 mL) were added formic acid (5.3 μL, 0.14 mmol), N,N-diisopropylethylamine (49 μL, 0.28 mmol) and bis(tri-tert-butylphosphine)palladium (0) (9.6 mg, 19 μmol) at room temperature, which was stirred under nitrogen atmosphere for 1 hour and 25 minutes at 100° C. Water and ethyl acetate were added to the reaction solution at room temperature, which was then filtered through a Celite pad. The filtrate was partitioned into water and ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% trifluoroacetic acid), and then further purified by silica gel column chromatography (heptane:ethyl acetate=1:1) to obtain the title compound (0.66 mg, 2.0%).

後処理

  1. filtrationwhich was then filtered through a Celite pad
  2. customThe filtrate was partitioned into water and ethyl acetate
  3. washThe organic layer was washed with water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under a reduced pressure
  6. customThe residue was purified by reverse-phase high performance liquid chromatography (
  7. additioncontaining 0.1% trifluoroacetic acid), and
  8. customthen further purified by silica gel column chromatography (heptane:ethyl acetate=1:1)

出典と根拠

ORDレコード
ord-bd89008e17654566bcef7f24a646eff9
出典データセット
uspto-grants-2013_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08507530B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート