N-Hydroxysuccinimide → 8-(3-(N-Norvalyl)amino-pyrrolidinyl)-4H-quinolizin-4-one-3-carboxylic acid

HRID 1080188

반응식

HRID 1080188 반응식
NC1CCN(CC2C=CC=CC=2)C1.C(OC(N[C@H](C(O)=O)CCC)=O)(C)(C)C.ON1C(=O)CCC1=O.Cl[C:38]1[CH:39]=[CH:40][N:41]2[C:46]([CH:47]=1)=[CH:45][CH:44]=[C:43]([C:48]([O:50]CC)=[O:49])[C:42]2=[O:53].C([NH:61][C@H:62]([C:66]([NH:68][CH:69]1[CH2:73][CH2:72][NH:71][CH2:70]1)=[O:67])[CH2:63][CH2:64][CH3:65])(OC(C)(C)C)=O>>[NH2:61][C@H:62]([C:66]([NH:68][CH:69]1[CH2:73][CH2:72][N:71]([C:38]2[CH:39]=[CH:40][N:41]3[C:46]([CH:47]=2)=[CH:45][CH:44]=[C:43]([C:48]([OH:50])=[O:49])[C:42]3=[O:53])[CH2:70]1)=[O:67])[CH2:63][CH2:64][CH3:65]

참가 물질

6

반응물 5

HCID 80170N-HydroxysuccinimideHCID 2733748(2S)-2-(((tert-butoxy)carbonyl)amino)pentanoic acidHCID 27566131-Benzyl-3-aminopyrrolidineHCID 3314858Ethyl 8-chloro-4-oxo-4H-quinolizine-3-carboxylateHCID 149991413-(N-Boc-norvalyl)aminopyrrolidine

생성물 1

HCID 228676868-(3-(N-Norvalyl)amino-pyrrolidinyl)-4H-quinolizin-4-one-3-carboxylic acid

실험 절차

3-Amino-1-benzylpyrrolidine (I. Sumio and T. Matsuo, Japanese Kokai JP 5328161, published Mar. 16, 1978) is coupled to N-t-butoxycarbonyl norvaline (Boc-nVal) using conventional N-hydroxysuccinimide coupling procedures. The 1-benzyl group is removed by hydrogenolysis in methanol using palladium on carbon catalyst. The 3-(N-Boc-norvalyl)aminopyrrolidine is then reacted with ethyl 8-chloro-4H-quinolizin-4-one-3-carboxylate, the product of Step 3 of Example 58, as described in Step 4 of Example 58, replacing 3-(N-t-butoxycarbonylamino)pyrrolidine with 3-(N-Boc-norvalyl)aminopyrrolidine, to give 8-(3-(N-norvalyl)amino-pyrrolidinyl)-4H-quinolizin-4-one-3-carboxylic acid with the nitrogen of the amino acid protected with a Boc group. The Boc protecting group is removed by standard hydrolysis using trifluoroacetic acid and dilute aqueous hydrochloric acid.

후처리

  1. customThe 1-benzyl group is removed by hydrogenolysis in methanol
  2. customThe 3-(N-Boc-norvalyl)aminopyrrolidine is then reacted with ethyl 8-chloro-4H-quinolizin-4-one-3-carboxylate

출처 및 근거

ORD 기록
ord-e8c80bbc63644a8a925c5a0718661831
출처 데이터셋
uspto-grants-1996_12
특허 번호
US05580872

연결된 노트

불러오는 중…