Diisopropylethylamine → 4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-{(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-[(3-fluorophenyl)methyl]ethyl}-5-(methyloxy)-2-thiophenecarboxamide

HRID 2392220노트

반응식

HRID 2392220 반응식
[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:17])[C:6]=1[C:7]1[CH:8]=[C:9]([C:14]([OH:16])=O)[S:10][C:11]=1[O:12][CH3:13].[NH2:18][C@@H:19]([CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=1)[CH2:20][N:21]1[C:29](=[O:30])[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22]1=[O:31].CC(OC(N[C@H](C(O)=O)CC1C=CC=CC=1C(F)(F)F)=O)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:17])[C:6]=1[C:7]1[CH:8]=[C:9]([C:14]([NH:18][C@@H:19]([CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=2)[CH2:20][N:21]2[C:29](=[O:30])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]2=[O:31])=[O:16])[S:10][C:11]=1[O:12][CH3:13]

참가 물질

7

반응물 5

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 2761473Boc-2-(trifluoromethyl)-L-phenylalanineHCID 578263844-(4-chloro-1-methyl-1H-pyrazol-5-yl)-5-(methyloxy)-2-thiophenecarboxylic AcidHCID 58226866(S)-2-(2-amino-3-(3-fluorophenyl)propyl)isoindoline-1,3-dione

생성물 1

HCID 578264224-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-{(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-[(3-fluorophenyl)methyl]ethyl}-5-(methyloxy)-2-thiophenecarboxamide수율 63%

시약·촉매·용매 1

HCID 6212Chloroform용매

실험 절차

To a 50 mL round-bottomed flask was added 4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-5-(methyloxy)-2-thiophenecarboxylic acid (220 mg, 0.81 mmol) [prepared according to the procedure of Example 188], 2-[(2S)-2-amino-3-(3-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione (281 mg, 0.84 mmol) [prepared according to the procedure of Preparation 6, except substituting N-{[(1,1-dimethylethyl)oxy]carbonyl}-3-fluoro-L-phenylalanine (5.03 g, 17.8 mmol) for N-{[(1,1-dimethylethyl)oxy]carbonyl}-2-(trifluoromethyl)-L-phenylalanine] and PyBrop (472 mg, 1.0 mmol) in Chloroform (8 mL). DIEA (710 μL, 4.07 mmol) was added and the reaction stirred overnight at room temperature. The mixture was adsorbed onto silica and purified via column chromatography (25-70% EtOAc/Hex) affording the title compound (281 mg, 0.51 mmol, 63%): LC-MS (ES) m/z=553 (M+H)+.

후처리

  1. customprepared
  2. customprepared
  3. customaccording to the procedure of Preparation 6
  4. custompurified via column chromatography (25-70% EtOAc/Hex)

출처 및 근거

ORD 기록
ord-3526ae1ed0934e2297b3df3f274c15f8
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08273782B2

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