O-Phenylenediamine → 2-[3-(2-Amino-phenylcarbamoylmethyl)-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-phenyl acetamide

HRID 343195노트

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HRID 343195 반응식
[CH:1]([C:4](C1C=CC=CC=1)(C(=O)N)[N:5]1[C:11](=[O:12])[C:10]([CH2:14][C:15]([OH:17])=O)([CH3:13])[C:9](=[O:18])[N:8](C2C=CC=CC=2)[C:7]2[CH:25]=[CH:26][CH:27]=[CH:28][C:6]1=2)([CH3:3])C.C(OC(C[C:49]1(CC(O)=O)[C:55](=[O:56])[N:54]([C:57]([CH:69](C)C)([C:61]2C=CC(OC)=CC=2)C(=O)N)[C:53]2[CH:72]=[CH:73][CH:74]=[CH:75][C:52]=2N(C2C=CC=CC=2)C1=O)=O)C1C=CC=CC=1.[C:87]1([NH2:94])[CH:92]=[CH:91][CH:90]=[CH:89][C:88]=1[NH2:93].F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1C[CH2:107][CH2:106][CH2:105]1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[NH2:93][C:88]1[CH:89]=[CH:90][CH:91]=[CH:92][C:87]=1[NH:94][C:15]([CH2:14][C:10]1([CH3:13])[C:9](=[O:18])[N:8]([CH2:49][C:55]([N:54]([CH:57]([CH3:61])[CH3:69])[C:53]2[CH:52]=[CH:75][CH:74]=[CH:73][CH:72]=2)=[O:56])[C:7]2[CH:25]=[CH:26][CH:27]=[CH:28][C:6]=2[N:5]([C:4]2[CH:107]=[CH:106][CH:105]=[CH:3][CH:1]=2)[C:11]1=[O:12])=[O:17]

참가 물질

7

반응물 5

HCID 7243O-PhenylenediamineHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 67696769[1-(isopropyl-phenyl-carbamoylmethyl)-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]acetic acidHCID 86753587{3-(Benzyloxycarbonyl-methyl)-1-[isopropyl-(4-methoxy-phenyl)-carbamoylmethyl]-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}acetic acid

생성물 1

HCID 676972962-[3-(2-Amino-phenylcarbamoylmethyl)-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-phenyl acetamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
50 °C

실험 절차

A stirring solution of 100 mg (0.20 mmol) of [1-(Isopropyl-phenyl-carbamoylmethyl)-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-acetic acid, prepared as in Intermediate 7, 32 mg (0.30 mmol, 1.5 equiv) of 1,2-phenylene diamine, 187 mg (0.40 mmol, 2.0 equiv) of bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBroP), and 80 mg (0.60 mmol, 3.0 equiv) of diisopropylethylamine in 2 mL of DMF is heated at 50° C. for 48 h. The DMF is removed in vacuo and the residue is dissolved in 20 mL of EtOAc and extracted with 20 mL 1N HCl. The organic layer is dried (MgSO4) and the solvent removed in vacuo. The resulting oil is purified by silica gel flash column chromatography using dichloromethane/MeOH 20/1 as eluent followed by further purification via reverse phase MPLC using a C-18 column and 60% acetonitrile/40% H2O with 0.1% TFA as eluent followed by lyophilization to afford 30 mg of the title compound as a white amorphous solid: 1H NMR (CDCl3, 300 MHz) δ9.38 (s, 0.7H), 9.17 (s, 0.3H), 7.53-7.04 (m, 17H), 6.81 (d, 1H, J=4.7), 4.97 (m, 1H), 4.57 (d, 0.5H, J=16.6), 4.27 (s, br, 2H), 3.87 (d, 0.5H, J=16.6), 3.36 (d, 1H, J=15.6), 3.13 (d, 1H, J=15.6), 2.60 (d, 0.5H, J=15.3), 2.42 (d, 0.5H, J=15.3), 1.61 (s, 1H), 1.22 (s, 2H), 1.09 (m, 6H); low resolution MS (FAB)m/e 590 (MH+), 482.

후처리

  1. customThe DMF is removed in vacuo
  2. dissolutionthe residue is dissolved in 20 mL of EtOAc
  3. extractionextracted with 20 mL 1N HCl
  4. dry with materialThe organic layer is dried (MgSO4)
  5. customthe solvent removed in vacuo
  6. customThe resulting oil is purified by silica gel flash column chromatography
  7. customfollowed by further purification via reverse phase MPLC

출처 및 근거

ORD 기록
ord-a22dfe043c31444e85885ce42874c5b0
출처 데이터셋
uspto-grants-1999_01
특허 번호
US05859007

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