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

HRID 2196418ノート

反応式

HRID 2196418 の反応式
[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:17])[C:6]=1[C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][C:8]=1[F:16].Cl.[NH2:19][C@@H:20]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[C:40]([F:43])([F:42])[F:41])[CH2:21][N:22]1[C:30](=[O:31])[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]1=[O:32].C(N(C(C)C)CC)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:17])[C:6]=1[C:7]1[CH:15]=[CH:14][C:10]([C:11]([NH:19][C@@H:20]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[C:40]([F:43])([F:41])[F:42])[CH2:21][N:22]2[C:30](=[O:31])[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23]2=[O:32])=[O:13])=[CH:9][C:8]=1[F:16]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 593549914-(4-chloro-1-methyl-1H-pyrazol-5-yl)-3-fluorobenzoic acidHCID 670654562-{(2s)-2-Amino-3-[2-(trifluoromethyl)phenyl]propyl}-1h-isoindole-1,3(2h)-dione-hcl

生成物 1

HCID 593550284-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-3-fluorobenzamide収率 36%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-3-fluorobenzoic acid (100 mg, 0.43 mmol), 2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione-HCl (151 mg, 0.43 mmol) [prepared according to Preparation 3], diisopropylethyl amine (0.4 mL, 2.14 mmol) in DCM (5 mL) was added PyBrop (330 mg, 0.71 mmol) in one portion. After 1 h, the reaction contents were partitioned between H2O/DCM. The aqueous phase was washed several times with DCM. The combined organic fractions were dried (Na2SO4), concentrated and purified via column chromatography (silica) affording the title compound (90 mg, 36%) as a white solid: LCMS (ES) m/z=585 (M+H)+.

後処理

  1. customthe reaction contents
  2. customwere partitioned between H2O/DCM
  3. washThe aqueous phase was washed several times with DCM
  4. dry with materialThe combined organic fractions were dried (Na2SO4)
  5. concentrationconcentrated
  6. custompurified via column chromatography (silica)

出典と根拠

ORDレコード
ord-63d7af49c5404fce82dfc064bd4f1665
出典データセット
uspto-grants-2012_12
特許番号
US08338434B2

反応ノート

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