(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

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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.

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