Diisopropylethylamine → 4,5-Difluoro-2-(2-iodo-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester

HRID 1047949ノート

反応式

HRID 1047949 の反応式
[I:1][C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.Cl.[CH2:13]([O:15][C:16]([C:18]1([NH2:29])[CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([F:28])[C:24]=2[F:27])[CH2:19]1)=[O:17])[CH3:14].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[CH2:13]([O:15][C:16]([C:18]1([NH:29][C:4](=[O:6])[C:3]2[CH:7]=[CH:8][CH:9]=[C:10]([CH3:11])[C:2]=2[I:1])[CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([F:28])[C:24]=2[F:27])[CH2:19]1)=[O:17])[CH3:14]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 27593652-Iodo-3-methylbenzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2 回HCID 685896422-amino-4,5-difluoro-indan-2-carboxylic acid ethyl ester HCl salt

生成物 1

HCID 593141704,5-Difluoro-2-(2-iodo-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester収率 79.5%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 2-iodo-3-methyl-benzoic acid (1.31 g, 5 mmol), 2-amino-4,5-difluoro-indan-2-carboxylic acid ethyl ester HCl salt (D7, 1.38 g, 5 mmol), HATU [O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium PF6, 3.8 g, 10 mmol) in anhydrous DMF (20 mL) is added DIPEA (N,N-diisopropylethylamine, 3.3 mL, 15 mmol). The resulting solution is stirred at room temperature for two days. After the removal of DMF in vacuo, the residue obtained is dissolved in ethyl acetate (200 mL) and washed with saturated NaHCO3 (1×100 mL) and brine (2×100 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The obtained residue is purified by flash column chromatography (24 g silica gel, gradient elution: 0%-50% EtOAc in heptane) to give a pure product (386) as white solid (1.93 g, 79%).

後処理

  1. customAfter the removal of DMF in vacuo
  2. customthe residue obtained
  3. washwashed with saturated NaHCO3 (1×100 mL) and brine (2×100 mL)
  4. dry with materialThe organic layer is dried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe obtained residue is purified by flash column chromatography (24 g silica gel, gradient elution: 0%-50% EtOAc in heptane)

出典と根拠

ORDレコード
ord-16119d42b5c54bdc98f1087868fbc03c
出典データセット
uspto-grants-2013_10
特許番号
US08569535B2

反応ノート

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