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1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl ((1S,4S)-4-(2-((tert-butyldimethylsilyl)oxy)ethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamate

HRID 1747119
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HRID 1747119 반응식
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][C@@:12]([CH2:17][CH2:18][O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])([C:14]([OH:16])=O)[CH:11]=[CH:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.Cl.Cl.[F:60][C:61]([F:73])([F:72])[C:62]1[CH:63]=[N:64][C:65]2[CH2:66][CH2:67][NH:68][CH2:69][C:70]=2[CH:71]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Si:20]([O:19][CH2:18][CH2:17][C@@:12]1([C:14]([N:68]2[CH2:67][CH2:66][C:65]3[N:64]=[CH:63][C:62]([C:61]([F:60])([F:72])[F:73])=[CH:71][C:70]=3[CH2:69]2)=[O:16])[CH2:13][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH:10]=[CH:11]1)([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:21])[CH3:22]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 6

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27960291-Hydroxybenzotriazole hydrateHCID 669114653-(Trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine--hydrogen chloride (1/2)HCID 86708128(1S,4S)-4-((tert-butoxycarbonyl)amino)-1-(2-((tert-butyldimethylsilyl)oxy)ethyl)cyclopent-2-enecarboxylic acid

생성물 1

HCID 86708130tert-butyl ((1S,4S)-4-(2-((tert-butyldimethylsilyl)oxy)ethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamate

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of the product of Step B (3.47 g, 8.99 mmol, 1 eq) in DCM (40 mL) at rt was added HOBt hydrate (2.34 g, 15.3 mmol, 1.7 eq) and EDCI (2.58 g, 13.5 mmol, 1.5 eq). After 15 min, DIEA (7.8 mL, 45.3 mmol, 5 eq) and 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-2 HCl (3.71 g, 13.5 mmol, 1 eq) were added and the solution stirred overnight at rt. Saturated NaHCO3 was added, the solution extracted with DCM, the organics combined, dried over MgSO4, and concentrated. Purification by chromatography (120 g column) eluting with 25 to 60% EtOAc/heptane afforded the title compound of Step C. 1H NMR (CHLOROFORM-d) δ: 8.71 (s, 1H), 7.69 (s, 1H), 6.19 (d, J=5.4 Hz, 1H), 5.76 (dd, J=5.6, 2.0 Hz, 1H), 4.68-4.86 (m, 4H), 3.85-4.07 (m, 2H), 3.54-3.65 (m, 2H), 3.13 (t, J=5.7 Hz, 2H), 2.58 (dd, J=13.3, 7.7 Hz, 1H), 1.98-2.16 (m, 2H), 1.85-1.97 (m, 1H), 1.42 (s, 9H), 0.84 (s, 9H), −0.02 (d, J=4.4 Hz, 6H). Calculated for C28H42F3N3O4Si: 570.3 (M+1). found: 570.3.

후처리

  1. extractionthe solution extracted with DCM
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customPurification by chromatography (120 g column)
  5. washeluting with 25 to 60% EtOAc/heptane

출처 및 근거

ORD 기록
ord-e300c1bdcb6b49d782ddf083c20ebe47
출처 데이터셋
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09150532B2

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