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llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
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Sodium Carbonate → (1R,3S,5R)-tert-butyl 3-(5-(4-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate

HRID 1471127
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HRID 1471127 반응식
[CH3:1][C:2]1([CH3:28])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:18]=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[C:14](B4OC(C)(C)C(C)(C)O4)[CH:15]=3)[CH:10]=2)[O:3]1.Br[C:30]1[CH:35]=[CH:34][C:33]([C:36]2[NH:40][C:39]([C@@H:41]3[CH2:46][C@@H:45]4[C@@H:43]([CH2:44]4)[N:42]3[C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])=[N:38][CH:37]=2)=[CH:32][CH:31]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:7][C:6]1([CH3:8])[C:2]([CH3:1])([CH3:28])[O:3][B:4]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH:15]=[C:14]([C:30]2[CH:35]=[CH:34][C:33]([C:36]4[NH:40][C:39]([C@@H:41]5[CH2:46][C@@H:45]6[C@@H:43]([CH2:44]6)[N:42]5[C:47]([O:49][C:50]([CH3:53])([CH3:51])[CH3:52])=[O:48])=[N:38][CH:37]=4)=[CH:32][CH:31]=2)[CH:13]=[CH:12]3)[O:5]1
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참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 57816594(1R,3S,5R)-tert-butyl 3-(5-(4-bromophenyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylateHCID 596108242,2'-(Naphthalene-2,6-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)

생성물 1

HCID 66982160(1R,3S,5R)-tert-butyl 3-(5-(4-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate수율 40.4%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

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온도
80 °C

실험 절차

A solution of 2,6-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalene (1.0 g, 2.6 mmol), (1R,3S,5R)-tert-butyl 3-(5-(4-bromophenyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (1.06 g, 2.63 mmol), Na2CO3 (0.837 g, 7.89 mmol) in DME (20 mL) and water (2 mL) was degassed under vacuum for 10 min. The mixture was heated at 80° C. and then Pd(Ph3P)4 (0.152 g, 0.132 mmol) was added under a stream of nitrogen. The reactor was sealed and the heating was pursued further at 120° C. for 16 h. The DME was removed in vacuo and the crude material was partitioned between EtOAc/H2O. The layers were separated and the aqueous layer was extracted several times with EtOAc. The combined organic extracts were dried over Na2SO4 and evaporated in vacuo. The residue was purified by flash column chromatography (BIOTAGE®), eluting with a gradient of 0 to 5% MeOH/DCM to afford the partially pure target product contaminated with reaction side products. The impure product was purified again by flash column chromatography (BIOTAGE®), eluting with a gradient of 50 to 100% EtOAc/hexanes, then the column was flushed with 10% MeOH/DCM to afford (1R,3S,5R)-tert-butyl 3-(5-(4-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (606 mg) as yellow foam. LC-MS retention time 1.608 min; m/z 578.4 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Sunfire 5u C18 4.6×30 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where Solvent A was 10% MeOH/90% H2O/0.1% TFA and Solvent B was 10% H2O/90% MeOH/0.1% TFA. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (500 MHz, chloroform-d, Partial NMR) δ ppm 4.89 (br s, 1H), 3.20-3.66 (m, 1H), 2.33-2.50 (m, 1H), 1.76-1.86 (m, 1H), 1.52 (br s, 9H), 1.24-1.32 (m, 12H), 0.87-0.93 (m, 1H), 0.51 (br s, 1H).

후처리

  1. customThe reactor was sealed
  2. customThe DME was removed in vacuo
  3. customthe crude material was partitioned between EtOAc/H2O
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted several times with EtOAc
  6. dry with materialThe combined organic extracts were dried over Na2SO4
  7. customevaporated in vacuo
  8. customThe residue was purified by flash column chromatography (BIOTAGE®)
  9. washeluting with a gradient of 0 to 5% MeOH/DCM
  10. customto afford the partially pure target product
  11. customcontaminated with reaction side products
  12. customThe impure product was purified again by flash column chromatography (BIOTAGE®)
  13. washeluting with a gradient of 50 to 100% EtOAc/hexanes
  14. customthe column was flushed with 10% MeOH/DCM

출처 및 근거

ORD 기록
ord-36bd967fa2a140cc85f7f0b4f8d34178
출처 데이터셋
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09006455B2

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