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Triphenylphosphine → Tert-butyl 3-{2-[(3,5-bis-trifluoromethyl-benzyl)-(5'-isopropyl-4,5,2'-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-propionate

HRID 604179
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인쇄 미리보기

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HRID 604179 반응식
[F:1][C:2]([F:45])([F:44])[C:3]1[CH:4]=[C:5]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[CH2:6][N:7]([CH2:15][C:16]1[CH:21]=[C:20]([O:22][CH3:23])[C:19]([O:24][CH3:25])=[CH:18][C:17]=1[C:26]1[CH:31]=[C:30]([CH:32]([CH3:34])[CH3:33])[CH:29]=[CH:28][C:27]=1[O:35][CH3:36])[C:8]1[N:13]=[CH:12][C:11]([OH:14])=[CH:10][N:9]=1.O[CH2:47][CH2:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1.[Cl-].[Na+].O>[F:45][C:2]([F:1])([F:44])[C:3]1[CH:4]=[C:5]([CH:37]=[C:38]([C:40]([F:41])([F:42])[F:43])[CH:39]=1)[CH2:6][N:7]([CH2:15][C:16]1[CH:21]=[C:20]([O:22][CH3:23])[C:19]([O:24][CH3:25])=[CH:18][C:17]=1[C:26]1[CH:31]=[C:30]([CH:32]([CH3:34])[CH3:33])[CH:29]=[CH:28][C:27]=1[O:35][CH3:36])[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:47][CH2:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])=[CH:12][N:13]=1
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7

반응물 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 16218743tert-Butyl 3-hydroxypropanoateHCID 866269112-[(3,5-Bis-trifluoromethyl-benzyl)-(5'-isopropyl-4,5,2'-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-ol

생성물 1

HCID 86626910
Tert-butyl 3-{2-[(3,5-bis-trifluoromethyl-benzyl)-(5'-isopropyl-4,5,2'-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-propionate
수율 59.6%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 57417360Sodium chloride; water용매

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온도
60 °C

실험 절차

2-[(3,5-Bis-trifluoromethyl-benzyl)-(5′-isopropyl-4,5,2′-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-ol (60 mg) is dissolved in tetrahydrofuran (1 ml) and thereto are added tert-butyl 3-hydroxy-propionate (336 mg) and triphenylphosphine (592 mg), and thereto is added dropwise diisopropyl azodicarboxylate (447 μl) and the mixture is stirred at 60° C. overnight. To the reaction mixture is added a saturated brine, and the mixture is extracted with ethyl acetate. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. To the resulting residue is added isopropylether and the insoluble material is filtered and the filtrate is concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=9:1→2:1) and NH-silica gel column chromatography (hexane:ethyl acetate=9:1→4:1) to give tert-butyl 3-{2-[(3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-4,5,2′-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-propionate (43 mg). MS (m/z): 764 [M+H]+

후처리

  1. extractionthe mixture is extracted with ethyl acetate
  2. washThe organic layer is washed with a saturated brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. additionTo the resulting residue is added isopropylether
  6. filtrationthe insoluble material is filtered
  7. concentrationthe filtrate is concentrated under reduced pressure
  8. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=9:1→2:1) and NH-silica gel column chromatography (hexane:ethyl acetate=9:1→4:1)

출처 및 근거

ORD 기록
ord-2e1600ca920b4098b07401a0f7d3abff
출처 데이터셋
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07906517B2

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