1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl(R)-1-((3aS,4R,6aR)-4-(2,2-dicyclohexylacetamido)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-4-methyl-1-oxopentan-2-ylcarbamate

HRID 1092565

반응식

HRID 1092565 반응식
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:14]([OH:16])=O)[CH2:10][CH:11]([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:17]1([CH:23]([CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]2)[C:24]([NH:26][C@H:27]2[C@H:34]3[C@H:30]([CH2:31][NH:32][CH2:33]3)[CH2:29][CH2:28]2)=[O:25])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.OC1C2N=NNC=2C=CC=1.CN(C)CCCN=C=NCC>ClCCl>[CH:35]1([CH:23]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[C:24]([NH:26][C@H:27]2[C@H:34]3[C@H:30]([CH2:31][N:32]([C:14](=[O:16])[C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:10][CH:11]([CH3:12])[CH3:13])[CH2:33]3)[CH2:29][CH2:28]2)=[O:25])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40]1

참가 물질

6

반응물 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 637604tert-Butoxycarbonyl-D-leucineHCID 546741702,2-dicyclohexyl-N-[(3aS,4R,6aR)-octahydrocyclopenta[c]pyrrol-4-yl]acetamideHCID 178418300HCID 178418300, 화합물

생성물 1

HCID 131729483tert-butyl(R)-1-((3aS,4R,6aR)-4-(2,2-dicyclohexylacetamido)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-4-methyl-1-oxopentan-2-ylcarbamate

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

N-(tert-Butoxycarbonyl)-D-leucine (72.7 mg, 0.314 mmol), 2,2-dicyclohexyl-N-[(3aS,4R,6aR)-octahydrocyclopenta[c]pyrrol-4-yl]acetamide (95 mg, 0.286 mmol) from Example 74, and hydroxybenzotriazole (48.1 mg, 0.314 mmol) were combined in dichloromethane (10 mL). After 20 minutes, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (0.056 mL, 0.314 mmol) was added, and the reaction mixture was stirred at room temperature for 18 hours. The reaction was quenched with water. The separated organic layer was reduced in volume, and the crude material was applied to a silica gel cartridge (Analogix®, Burlington, Wis., RS-12) and eluted first with 10% to 100% ethyl acetate/hexanes and then with 1-10% methanol (2 N ammonia)/dichloromethane to give tert-butyl(R)-1-((3aS,4R,6aR)-4-(2,2-dicyclohexylacetamido)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-4-methyl-1-oxopentan-2-ylcarbamate: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.26 (dd, J=7.2, 24.0, 1H), 7.91 (d, J=8.6, 1H), 4.48-4.36 (m, 1H), 4.12-3.96 (m, 1H), 3.87 (dd, J=7.4, 10.3, 1H), 3.70 (ddd, J=8.0, 14.4, 23.7, 1H), 3.40 (dd, J=5.7, 12.3, 1H), 2.77 (s, 1H), 2.58 (d, J=6.1, 1H), 2.08 (s, 1H), 2.01 (dd, J=5.6, 10.4, 2H), 1.96-1.55 (m, 17H), 1.54-1.50 (m, 9H), 1.49-1.37 (m, 2H), 1.19 (qdd, J=12.3, 22.3, 24.7, 11H), 1.00 (t, J=6.6, 3H), 0.88 (d, J=6.6, 1H).

후처리

  1. customThe reaction was quenched with water
  2. washeluted first with 10% to 100% ethyl acetate/hexanes

출처 및 근거

ORD 기록
ord-320bc4fc329e4f45a24332e01f4b3703
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129417B2

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