Triethylamine → tert-butyl(S)-3-(6-tert-butoxycarbonylaminopyridin-3-yl)-2-[3-((9S,12R)-9-isopropyl-11-oxo-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-12-yl)ureido]propionate

HRID 2040008노트

반응식

HRID 2040008 반응식
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[NH2:13][C@@H:14]([CH2:22][C:23]1[CH:24]=[N:25][C:26]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:27][CH:28]=1)[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].C(N(CC)CC)C.[NH2:44][C@@H:45]1[CH2:60][C:59]2=[CH:61][CH:62]=[C:56]([CH:57]=[CH:58]2)[O:55][CH2:54][CH2:53][CH2:52][CH2:51][O:50][CH2:49][C@H:48]([CH:63]([CH3:65])[CH3:64])[NH:47][C:46]1=[O:66]>CN(C=O)C>[C:33]([O:32][C:30]([NH:29][C:26]1[N:25]=[CH:24][C:23]([CH2:22][C@H:14]([NH:13][C:1]([NH:44][C@@H:45]2[CH2:60][C:59]3=[CH:58][CH:57]=[C:56]([CH:62]=[CH:61]3)[O:55][CH2:54][CH2:53][CH2:52][CH2:51][O:50][CH2:49][C@H:48]([CH:63]([CH3:64])[CH3:65])[NH:47][C:46]2=[O:66])=[O:2])[C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])=[CH:28][CH:27]=1)=[O:31])([CH3:36])([CH3:35])[CH3:34]

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 58360483(9S,12R)-12-Amino-9-isopropyl-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-11-oneHCID 58360487tert-Butyl (S)-2-amino-3-(6-tert-butoxycarbonylaminopyridin-3-yl)propionate

생성물 1

HCID 67320386tert-butyl(S)-3-(6-tert-butoxycarbonylaminopyridin-3-yl)-2-[3-((9S,12R)-9-isopropyl-11-oxo-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-12-yl)ureido]propionate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

112 mg (0.69 mmol) of 1,1′-carbonyldiimidazole were added to a mixture of 234 mg (0.69 mmol) of tert-butyl (S)-2-amino-3-(6-tert-butoxycarbonylaminopyridin-3-yl)-propionate and 106 μl (77 mg, 0.76 mmol) of triethylamine in 2.5 ml of DMF. The solution was stirred at RT for 1 h, before a solution of 222 mg (0.69 mmol) of (9S,12R)-12-amino-9-isopropyl-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-11-one (1-1E) in 2.5 ml of DMF was added. The mixture was left to stand overnight and then concentrated and partitioned between water and ethyl acetate. The organic phase was separated off, dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative HPLC. The required fractions were combined, freed of acetonitrile, made slightly alkaline with sodium bicarbonate and extracted with ethyl acetate. The organic phase was dried over sodium sulfate, filtered and concentrated.

후처리

  1. additionwas added
  2. waitThe mixture was left
  3. concentrationconcentrated
  4. custompartitioned between water and ethyl acetate
  5. customThe organic phase was separated off
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by preparative HPLC
  10. extractionextracted with ethyl acetate
  11. dry with materialThe organic phase was dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated

출처 및 근거

ORD 기록
ord-81a800256c274d5f947adc2483678a35
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08580777B2

반응 노트

불러오는 중…