(R)-methyl 2-amino-3-methylbutanoate → (R)-2-{(R)-2-[4-(4-Chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5lambda4-thieno[3,2-d]pyrimidin-4-ylamino}-3-methyl-butyric acid methyl ester

HRID 243640

Reaktionsgleichung

Reaktionsgleichung von HRID 243640
ClC1C=CC(N2CCN(C3N=C(N[C@H](C(C)C)CO)C4[S@](=O)CCC=4N=3)CC2)=CC=1.Cl[C:32]1[C:33]2[S@:53](=[O:54])[CH2:52][CH2:51][C:34]=2[N:35]=[C:36]([N:38]2[CH2:43][CH2:42][N:41]([C:44]3[CH:49]=[CH:48][C:47]([Cl:50])=[CH:46][CH:45]=3)[CH2:40][CH2:39]2)[N:37]=1.[CH3:55][O:56][C:57](=[O:63])[C@@H:58]([CH:60]([CH3:62])[CH3:61])[NH2:59]>>[CH3:55][O:56][C:57](=[O:63])[C@H:58]([NH:59][C:32]1[C:33]2[S@:53](=[O:54])[CH2:52][CH2:51][C:34]=2[N:35]=[C:36]([N:38]2[CH2:43][CH2:42][N:41]([C:44]3[CH:45]=[CH:46][C:47]([Cl:50])=[CH:48][CH:49]=3)[CH2:40][CH2:39]2)[N:37]=1)[CH:60]([CH3:62])[CH3:61]

Komponenten

4

Edukt 3

HCID 2305648(R)-methyl 2-amino-3-methylbutanoateHCID 25266380(R)-2-{(R)-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5lambda4-thieno[3,2-d]pyrimidin-4-ylamino}-3-methyl-butan-1-olHCID 86645100(R)-4-chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine-5-oxide

Produkt 1

HCID 25266381(R)-2-{(R)-2-[4-(4-Chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5lambda4-thieno[3,2-d]pyrimidin-4-ylamino}-3-methyl-butyric acid methyl esterAusbeute 85 %

Versuchsvorschrift

The procedure for the formation of (R)-2-{(R)-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5λ4-thieno[3,2-d]pyrimidin-4-ylamino}-3-methyl-butan-1-ol (with the exception of omitting the IPA recrystallization) was followed, starting with (R)-4-chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine-5-oxide and D-valine methyl ester (1.3 equiv). This resulted in the crude product being obtained in 85% yield. 1H NMR (500 MHz, CDCl3) δ 7.18-7.26 (m, 2H), 6.82-6.90 (m, 2H), 5.78 (d, J=6.5 Hz, 1H), 4.59 (dd, J=7.0, 7.0 Hz, 1H), 3.98 (bs, 4H), 3.72 (s, 3H), 3.62 (ddd, J=7.5, 7.5, 15.0 Hz, 1H), 3.36 (ddd, J=8.0, 8.0, 15.0 Hz, 1H), 3.10-3.20 (m, 4H), 2.95-3.10 (m 2H), 2.23 (m, 1H), 1.00-1.07 (m, 6H); 13C NMR (500 MHz, CDCl3) δ 174.8, 172.8, 163.1, 159.8, 150.2, 129.4, 125.4, 118.0, 109.0, 59.6, 59.5, 52.3, 50.4, 49.7, 44.1, 33.0, 31.3, 19.4, 19.1 (3 signals missing due to overlap). LCMS (ESI) for C22H29ClN5O3S (M+H)+: calcd. 478.2, obsvd. 478.1.

Aufarbeitung

  1. customthe IPA recrystallization)

Quellen und Nachweise

ORD-Eintrag
ord-e60c96581f684be3b422a24fc862e879
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653282B2

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