1,3-Dibromobenzene → (NZ,3R)-N-[3-(3-bromophenyl)-5-methyl-1,3-thiazol-2-ylidene]-3-fluoropyrrolidine-1-carboxamide

HRID 390716

반응식

HRID 390716 반응식
[F:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([NH:9][C:10]2[S:11][C:12]([CH3:15])=[CH:13][N:14]=2)=[O:8])[CH2:3]1.ClC1C=C2C(N=CC=C2)=C2C=1C=CC=N2.C(=O)([O-])[O-].[Cs+].[Cs+].[Br:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40](Br)[CH:39]=1.[OH-].[NH4+].O>CN1CCCC1=O>[Br:37][C:38]1[CH:39]=[C:40]([N:14]2[CH:13]=[C:12]([CH3:15])[S:11]/[C:10]/2=[N:9]\[C:7]([N:4]2[CH2:5][CH2:6][C@@H:2]([F:1])[CH2:3]2)=[O:8])[CH:41]=[CH:42][CH:43]=1

참가 물질

7

반응물 5

HCID 79271,3-DibromobenzeneHCID 10796Cesium carbonateHCID 778655-Chloro-1,10-phenanthrolineHCID 86589665Water ammonium hydroxideHCID 86631926(3R)-3-fluoro-N-(5-methyl-1,3-thiazol-2-yl)pyrrolidine-1-carboxamide

생성물 1

HCID 42644892(NZ,3R)-N-[3-(3-bromophenyl)-5-methyl-1,3-thiazol-2-ylidene]-3-fluoropyrrolidine-1-carboxamide

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
120 °C

실험 절차

In a 4 mL vial charged with a stir bar, (3R)-3-fluoro-N-(5-methyl-1,3-thiazol-2-yl)pyrrolidine-1-carboxamide (40 mg, 0.17 mmol, Example 34A) was added, followed by copper(I) trifluoromethanesulfonate benzene complex (17 mg, 0.03 mmol), 5-chloro-1,10-phenanthroline (15 mg, 0.07 mmol) and cesium carbonate (61 mg, 0.19 mmol). A loose cap with septum was placed on the vial and then the vial was placed under vacuum in a vacuum oven for 30 minutes. The mixture was purged with nitrogen gas a couple of times. 1,3-Dibromobenzene (47 mg, 0.2 mmol) dissolved in 1-methyl-2-pyrrolidinone (1.0 mL) was added to the mixture. The vial was capped and placed on a heater/stirrer and heated to 120° C. overnight. Then 1 mL of a solution of concentrated ammonium hydroxide/water (1:2) was added. The reaction was filtered and concentrated to dryness. The residue was purified by reverse phase HPLC (C8, gradient 10-100% acetonitrile/water/0.1% trifluoroacetic acid) to provide the title compound.

후처리

  1. additionIn a 4 mL vial charged with a stir bar
  2. customA loose cap with septum
  3. customThe mixture was purged with nitrogen gas a couple of times
  4. additionwas added to the mixture
  5. customThe vial was capped
  6. customplaced on a heater/stirrer
  7. filtrationThe reaction was filtered
  8. concentrationconcentrated to dryness
  9. customThe residue was purified by reverse phase HPLC (C8, gradient 10-100% acetonitrile/water/0.1% trifluoroacetic acid)

출처 및 근거

ORD 기록
ord-277e0560c39b4dcc9d18ab741e2d1fa4
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08383657B2

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