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

HRID 1850

Reaction equation

HRID 1850 reaction equation
NC1CCN([CH2:7][C:8]2C=C[CH:11]=[CH:10][CH:9]=2)C1.C([O:18][C:19](N[C@H](C(O)=O)C)=[O:20])(C)(C)C.O[N:28]1[C:32](=[O:33])[CH2:31][CH2:30][C:29]1=O.C([NH:42][C@H:43]([C:45]([NH:47][CH:48]1[CH2:52][CH2:51][NH:50][CH2:49]1)=[O:46])[CH3:44])(OC(C)(C)C)=O>>[NH2:42][C@H:43]([C:45]([NH:47][CH:48]1[CH2:52][CH2:51][N:50]([C:9]2[CH:10]=[CH:11][N:28]3[C:7]([CH:8]=2)=[CH:29][CH:30]=[C:31]([C:19]([OH:20])=[O:18])[C:32]3=[O:33])[CH2:49]1)=[O:46])[CH3:44]

Participants

5

Reactant 4

HCID 80170N-HydroxysuccinimideHCID 85082Tert-butoxycarbonylalanineHCID 27566131-Benzyl-3-aminopyrrolidineHCID 145554503-(N-Boc-alanyl)aminopyrrolidine

Product 1

HCID 228676858-(3-(N-alanyl)amino-pyrrolidinyl)-4H-quinolizin-4-one-3-carboxylic acid

Procedure

3-Amino-1-benzylpyrrolidine (I. Sumio and T. Matsuo, Japanese Kokai JP 5328161, published Mar. 16, 1978) is coupled to N-t-butoxycarbonyl alanine (Boc-Ala) 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-alanyl)aminopyrrolidine is then reacted with ethyl 8-chloro-1-ethyl-4H-quinolizin-4-one-3-carboxylate, the product of Step 3 of Example 62, as described in Step 4 of Example 62 replacing 3-(N-t-butoxycarbonylaminopyrrolidine) with 3-(N-Boc-alanyl)aminopyrrolidine, to give 8-(3-(N-alanyl)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.

Workup

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

Sources & evidence

ORD record
ord-919d466c679b402eab41fc7f145b2864
Source dataset
uspto-grants-1998_03
Patent number
US05726182

Linked notes

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