Sodium Bicarbonate → HCID 178451930, 화합물

HRID 625587노트

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HRID 625587 반응식
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH:15]=[C:14]([C:19]2[NH:23][C:22]([C@@H:24]4[CH2:28][CH2:27][CH2:26][N:25]4[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[N:21][CH:20]=2)[CH:13]=[CH:12]3)O1.Br[C:38]1[CH:39]=[C:40]2[C:60](=[CH:61][CH:62]=1)[C:44]1[NH:45][C:46]([C@@H:48]3[CH2:52][CH2:51][CH2:50][N:49]3[C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])=[N:47][C:43]=1[CH2:42][CH2:41]2.C(=O)(O)[O-].[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>[C:32]([O:31][C:29]([N:25]1[CH2:26][CH2:27][CH2:28][C@H:24]1[C:22]1[NH:23][C:19]([C:14]2[CH:15]=[C:16]3[C:11](=[CH:12][CH:13]=2)[CH:10]=[C:9]([C:38]2[CH:39]=[C:40]4[C:60](=[CH:61][CH:62]=2)[C:44]2[NH:45][C:46]([C@@H:48]5[CH2:52][CH2:51][CH2:50][N:49]5[C:53]([O:55][C:56]([CH3:58])([CH3:57])[CH3:59])=[O:54])=[N:47][C:43]=2[CH2:42][CH2:41]4)[CH:18]=[CH:17]3)=[CH:20][N:21]=1)=[O:30])([CH3:35])([CH3:33])[CH3:34]

참가 물질

7

반응물 3

HCID 516892Sodium BicarbonateHCID 584986761,1-Dimethylethyl (2S)-2-[5-[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthalenyl]-1H-imidazol-2-yl]-1-pyrrolidinecarboxylateHCID 178451906HCID 178451906, 화합물

생성물 1

HCID 178451930HCID 178451930, 화합물수율 31.8%

시약·촉매·용매 3

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

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온도
80 °C

실험 절차

A solution of (S)-tert-butyl 2-(5-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (402 mg, 0.821 mmol), (S)-tert-butyl 2-(7-bromo-4,5-dihydro-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (344 mg, 0.821 mmol) and sodium bicarbonate (207 mg, 2.46 mmol) in DME (14 mL) and water (1.8 mL) was degassed under vacuum for 10 min. The mixture was heated at 80° C. at which time the flask was opened and Pd(Ph3P)4 (76 mg, 0.066 mmol) was added. The flask was flushed with nitrogen, sealed and heated at 120° C. for 16 h. The flask was cooled to room temp., the DME was removed in vacuo and the crude material was partitioned between DCM and H2O. The layers were separated and the aqueous layer was extracted several times with DCM. 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 20 to 100% EtOAc/Hexanes and then 0 to 10% methanol/DCM to afford (S)-tert-butyl 2-(7-(6-(2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)-4,5-dihydro-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (183 mg). LC-MS retention time 1.543 min; m/z 701.47 (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.

후처리

  1. customThe flask was flushed with nitrogen
  2. customsealed
  3. temperatureheated at 120° C. for 16 h
  4. temperatureThe flask was cooled to room temp.
  5. customthe DME was removed in vacuo
  6. customthe crude material was partitioned between DCM and H2O
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted several times with DCM
  9. dry with materialThe combined organic extracts were dried over Na2SO4
  10. customevaporated in vacuo
  11. customThe residue was purified by flash column chromatography (BIOTAGE®)
  12. washeluting with a gradient of 20 to 100% EtOAc/Hexanes

출처 및 근거

ORD 기록
ord-aa6cf55189824ed2ba11fa1dc00567bb
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09303007B2

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