Triethylamine → tert-butyl (2S)-2-[(1R,2R)-3-{[2-(cyclohepta-2,4,6-trien-1-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidine-1-carboxylate

HRID 74752노트

반응식

HRID 74752 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C@H:13]([O:19][CH3:20])[C@@H:14]([CH3:18])[C:15]([OH:17])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[CH:52]1([CH2:59][CH2:60][NH2:61])[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=[CH:53]1>ClCCl.CN(C)C=O>[CH:52]1([CH2:59][CH2:60][NH:61][C:15](=[O:17])[C@H:14]([CH3:18])[C@H:13]([C@@H:9]2[CH2:10][CH2:11][CH2:12][N:8]2[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[O:19][CH3:20])[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=[CH:53]1

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11033491(2R,3R)-3-((2S)-1-(tert-Butoxycarbonyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanoic acidHCID 236233082-(Cyclohepta-2,4,6-trien-1-yl)ethanamine

생성물 1

HCID 86685734tert-butyl (2S)-2-[(1R,2R)-3-{[2-(cyclohepta-2,4,6-trien-1-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidine-1-carboxylate수율 59%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

To a solution of #11 (3.57 g, 12.4 mmol, 1 eq.) in dichloromethane (100 mL, 0.1 M) and N,N-dimethylformamide (4 mL) was added HATU (5.36 g, 13.7 mmol, 1.1 eq.). After 20 minutes, triethylamine (5.20 mL, 37.3 mmol, 3 eq.) was added, followed by #62 (1.68 g, 12.4 mmol, 1 eq.), and the mixture was stirred for 18 hours. The reaction was concentrated in vacuo and the residue was taken up in ethyl acetate and washed with water (50 mL). The aqueous layer was back-extracted with ethyl acetate (3 times) and the combined organic layers were dried, filtered, and concentrated in vacuo to provide a brown oil, which was purified by silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane) to provide #63 (2.95 g, 59% yield) as a viscous oil. LC-MS: m/z 405.4 [M+H+], 427.4 [M+Na+], retention time=0.75 minutes; 1H NMR (400 MHz, CDCl3), presumed to be a mixture of rotamers: δ 6.63-6.68 (m, 2H), 6.16-6.23 (m, 2H), 5.19 (br dd, J=9.0, 5.8 Hz, 2H), 3.51-3.63 and 3.71-3.90 (2 br multiplets, total 3H), 3.42 (s, 3H), 3.18-3.29 and 3.34-3.47 (2 br multiplets, total 3H), 2.27-2.45 (br m, 1H), 1.6-2.00 (m, 7H), 1.47 and 1.50 (2 br s, total 9H), 1.16-1.29 (br m, 3H).

후처리

  1. concentrationThe reaction was concentrated in vacuo
  2. washwashed with water (50 mL)
  3. extractionThe aqueous layer was back-extracted with ethyl acetate (3 times)
  4. customthe combined organic layers were dried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto provide a brown oil, which
  8. customwas purified by silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane)

출처 및 근거

ORD 기록
ord-a47a1183c6234ec0b093586120941378
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08828401B2

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