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Acetic Acid → 5-(3-methyl-4-isothiazolyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione

HRID 1925070
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HRID 1925070 반응식
[CH3:1][C:2]1[C:6]([C:7]2[C:8](=[O:18])[NH:9][C:10](=[O:17])[N:11]([CH2:13][CH2:14][CH:15]=O)[CH:12]=2)=[CH:5][S:4][N:3]=1.[F:19][C:20]([F:34])([F:33])[C:21]1[CH:26]=[CH:25][C:24]([C@:27]23[CH2:32][C@H:31]2[CH2:30][NH:29][CH2:28]3)=[CH:23][CH:22]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[CH3:1][C:2]1[C:6]([C:7]2[C:8](=[O:18])[NH:9][C:10](=[O:17])[N:11]([CH2:13][CH2:14][CH2:15][N:29]3[CH2:30][C@H:31]4[C@:27]([C:24]5[CH:23]=[CH:22][C:21]([C:20]([F:19])([F:34])[F:33])=[CH:26][CH:25]=5)([CH2:32]4)[CH2:28]3)[CH:12]=2)=[CH:5][S:4][N:3]=1
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참가 물질

7

반응물 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexaneHCID 594483533-[5-(3-methyl-4-isothiazolyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]propanal

생성물 1

HCID 25253445
5-(3-methyl-4-isothiazolyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione
수율 14.5%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

실험 절차

3-[5-(3-methyl-4-isothiazolyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]propanal (Prep 0.126 mmol) was dissolved in 1,2-Dichloroethane (DCE) (1 ml). (1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (P4, 28.6 mg, 0.126 mmol) and ACETIC ACID (0.022 ml, 0.378 mmol) were added and the mixture was stirred at rt for 15 minutes. Then it was cooled at 0° C. and SODIUM TRIACETOXYBOROHYDRIDE (29.4 mg, 0.139 mmol) was added. The mixture was stirred at 0° C. for 3 hours. The mixture was treated with NaHCO3 aqueous saturated solution (5 mL) and extracted with DCM (3×5 mL). The organic were filtered on a separatory cartridge, combined and dried to afford a crude that was submitted to LC preparative purification. Fraction collected was dried (rotary) to afford the title compound as a white solid (8.7 mg, 14% yield).

후처리

  1. temperatureThen it was cooled at 0° C.
  2. stirringThe mixture was stirred at 0° C. for 3 hours
  3. extractionextracted with DCM (3×5 mL)
  4. filtrationThe organic were filtered on a separatory cartridge
  5. customdried
  6. customto afford a crude that
  7. customwas submitted to LC preparative purification
  8. customFraction collected
  9. customwas dried (rotary)

출처 및 근거

ORD 기록
ord-e9609c14413249dca5b966f7c2b46bf7
출처 데이터셋
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08178549B2

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