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

HRID 1047949노트

반응식

HRID 1047949 반응식
[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]

참가 물질

7

반응물 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)2회HCID 685896422-amino-4,5-difluoro-indan-2-carboxylic acid ethyl ester HCl salt

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-16119d42b5c54bdc98f1087868fbc03c
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08569535B2

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