Dimethylbarbituric acid → Allyl 4-[({(2S,4R)-1-{(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]-2-propenoyl}-4-[1-(methylsulfonyl)-4-piperidinyl]-2-pyrrolidinyl}carbonyl)amino]benzoate

HRID 1053845Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1053845
CC(O[C:6]([N:8]1[CH2:12][C@@H:11]([CH:13]2[CH2:18][CH2:17][N:16]([S:19]([CH3:22])(=[O:21])=[O:20])[CH2:15][CH2:14]2)[CH2:10][C@H:9]1[C:23]([OH:25])=[O:24])=[O:7])(C)C.[NH2:26][C:27]1[CH:38]=[CH:37][C:30]([C:31]([O:33][CH2:34][CH:35]=[CH2:36])=[O:32])=[CH:29][CH:28]=1.[Cl:39][C:40]1[CH:41]=[CH:42][C:43]([N:51]2[CH:55]=[N:54][N:53]=[N:52]2)=[C:44](/[CH:46]=[CH:47]/[C:48]([OH:50])=O)[CH:45]=1.CN1C(=O)CC(=O)N(C)C1=O>CN(C)C=O.C(OC(C)C)(C)C.ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:39][C:40]1[CH:41]=[CH:42][C:43]([N:51]2[CH:55]=[N:54][N:53]=[N:52]2)=[C:44](/[CH:46]=[CH:47]/[C:6]([N:8]2[CH2:12][C@@H:11]([CH:13]3[CH2:14][CH2:15][N:16]([S:19]([CH3:22])(=[O:20])=[O:21])[CH2:17][CH2:18]3)[CH2:10][C@H:9]2[C:23]([NH:26][C:27]2[CH:28]=[CH:29][C:30]([C:31]([O:33][CH2:34][CH:35]=[CH2:36])=[O:32])=[CH:37][CH:38]=2)=[O:25])=[O:7])[CH:45]=1.[Cl:39][C:40]1[CH:41]=[CH:42][C:43]([N:51]2[CH:55]=[N:54][N:53]=[N:52]2)=[C:44](/[CH:46]=[CH:47]/[C:48]([N:8]2[CH2:12][C@@H:11]([CH:13]3[CH2:18][CH2:17][N:16]([S:19]([CH3:22])(=[O:21])=[O:20])[CH2:15][CH2:14]3)[CH2:10][C@H:9]2[C:23]([NH:26][C:27]2[CH:28]=[CH:29][C:30]([C:31]([OH:33])=[O:32])=[CH:37][CH:38]=2)=[O:24])=[O:50])[CH:45]=1

Komponenten

10

Edukt 4

HCID 69860Dimethylbarbituric acidHCID 13075143Prop-2-en-1-yl 4-aminobenzoateHCID 66698416(E)-3-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)acrylic acidHCID 118107723(2S,4R)-1-{[(2-methyl-2-propanyl)oxy]carbonyl}-4-[1-(methylsulfonyl)-4-piperidinyl]-2-pyrrolidinecarboxylic acid

Produkt 2

HCID 90022958Allyl 4-[({(2S,4R)-1-{(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]-2-propenoyl}-4-[1-(methylsulfonyl)-4-piperidinyl]-2-pyrrolidinyl}carbonyl)amino]benzoateHCID 900238494-[({(2S,4R)-1-{(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]-2-propenoyl}-4-[1-(methylsulfonyl)-4-piperidinyl]-2-pyrrolidinyl}carbonyl)amino]benzoic acid

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysator2×HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 7914Diisopropyl EtherLösungsmittel

Versuchsvorschrift

Allyl 4-[({(2S,4R)-1-{(2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]-2-propenoyl}-4-[1-(methylsulfonyl)-4-piperidinyl]-2-pyrrolidinyl}carbonyl)amino]benzoate was prepared by following the procedures described in Examples 5, 9 and 8 starting from the compound prepared in Example 63. (Note: in the step corresponding to Example 5, allyl 4-aminobenzoate was used in place of tert-butyl 4-aminobenzoate. In the step corresponding to Example 8, (2E)-3-[5-chloro-2-(1H-tetrazol-1-yl)phenyl]acrylic acid was used in place of 1-(N,N′-bis(tert-butoxycarbonyl)carbamimidoyl)piperidine-4-carboxylic acid). After that, to a solution of the crude allyl ester (48 mg) in N,N-dimethylformamide (1 mL) was added tetrakis(triphenylphosphine)palladium(0) (2 mg) and 1,3-dimethylbarbituric acid (4 mg) and the reaction stirred overnight at room temperature. Further tetrakis(triphenylphosphine)palladium(0) (3 mg) was added at this juncture and stirring continued at room temperature for 7 h. The reaction mixture was left to stand overnight, diluted with a 1:1 mixture of diisopropylether and dichloromethane (1 mL) and the resulting precipitate collected by filtration. The yellow powder obtained was washed with dichloromethane and dried to give the title compound having the following physical properties (25 mg).

Aufarbeitung

  1. stirringstirring
  2. waitcontinued at room temperature for 7 h
  3. waitThe reaction mixture was left
  4. waitto stand overnight
  5. filtrationthe resulting precipitate collected by filtration
  6. customThe yellow powder obtained
  7. washwas washed with dichloromethane
  8. customdried

Quellen und Nachweise

ORD-Eintrag
ord-3a2aea6c3f074dc2b1e960cc3ceb87ac
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394250B2

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