Carbamic Acid → (s,s)-n-{1-[1-(5-Fluoro-2,3-dihydro-indol-1-ylmethyl)-3-ureido-propylcarbamoyl]-3-methyl-butyl}-3-methyl-benzamide

HRID 132140

반응식

HRID 132140 반응식
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C@@H:12]([NH:18][C:19](=[O:35])[C@@H:20]([NH:25][C:26](=[O:34])[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([CH3:33])[CH:28]=1)[CH2:21][CH:22]([CH3:24])[CH3:23])[CH2:13][CH2:14]C(O)=O)[CH2:6][CH2:5]2.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C([N:55](CC)CC)C.[N-:60]=[C:61]=[O:62].C(=O)(O)N.[N-]=[N+]=[N-]>CC(O)(C)C>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C@@H:12]([NH:18][C:19]([C@@H:20]([NH:25][C:26](=[O:34])[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([CH3:33])[CH:28]=1)[CH2:21][CH:22]([CH3:23])[CH3:24])=[O:35])[CH2:13][CH2:14][NH:60][C:61]([NH2:55])=[O:62])[CH2:6][CH2:5]2

참가 물질

8

반응물 6

HCID 277Carbamic AcidHCID 8471TriethylamineHCID 33558AzideHCID 105034IsocyanateHCID 199401P,P-Diphenylphosphinic azideHCID 11386148HCID 11386148, 화합물

생성물 1

HCID 11283381(s,s)-n-{1-[1-(5-Fluoro-2,3-dihydro-indol-1-ylmethyl)-3-ureido-propylcarbamoyl]-3-methyl-butyl}-3-methyl-benzamide수율 20%

시약·촉매·용매 1

HCID 6386tert-Butanol용매

반응 조건

온도
90 °C

실험 절차

The title compound of Example 43 (58.8 mg, 121 μmol) was treated with tBuOH (2 mL), diphenylphosphoryl azide (70 mg, 254 μmol) and triethylamine (60 mg, 592 mmol). The reaction was heated at 90° C. for 3 hours and cooled to rt. HPLC-MS analysis indicated that the Curtius rearrangement had occurred, but that the intermediate isocyanate had been hydrolyzed to the carbamic acid and activated as the azide rather than being intercepted by the alcohol. The solvent was removed and the reaction was extractively worked up with ethyl acetate and water, dried over MgSO4 and rotary evaporated. The residue was treated with concentrated ammonia and allowed to stir overnight. The reaction was again extractively worked up and then chromatographed on silica gel using DCM an MeOH as eluent to afford the title material (12 mg, 20%); 1H NMR (CDCl3, 400 MHz) δ 0.88 (d, 3H, J=6.3), 0.91 (d, 3H, J=6.3), 1.55-1.80 (m, 4H), 1.85-1.95 (m, 1H), 2.37 (s, 3H), 2.90-3.03 (m, 3H), 3.06-3.26 (m, 2H), 3.37 (dd, 1H, J1=8.7, J2=17.1), 3.48-3.61 (m, 2H), 4.01-4.26 (m, 1H), 4.26-4.38 (m, 1H), 4.50 (dd, 1H, J1=7.7, J2=15.0), 6.00-6.20 (m, 1H), 6.49 (dd, 1H, J1=4.0, J2=8.4), 6.74 (ddd, 1H, J1=2.5, J2=J3=8.9), 6.78-6.83 (m, 1H), 7.16-7.20 (m, 1H), 7.23-7.37 (m, 3H), 7.50-7.57 (m, 2H).

후처리

  1. temperaturecooled to rt
  2. customThe solvent was removed
  3. dry with materialdried over MgSO4 and rotary evaporated
  4. additionThe residue was treated with concentrated ammonia
  5. customchromatographed on silica gel

출처 및 근거

ORD 기록
ord-ec7b61ff3efe4d9abdb1ea600d3d8620
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07384970B2

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