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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
ノート
印刷プレビュー

反応式

HRID 1747119 の反応式
[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]
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e300c1bdcb6b49d782ddf083c20ebe47
出典データセット
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09150532B2

反応ノート

読み込み中…

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