Dimethyl Sulfoxide → (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-ol

HRID 243641

Reaction equation

HRID 243641 reaction equation
Cl[C:2]1[C:3]2[S@:23](=[O:24])[CH2:22][CH2:21][C:4]=2[N:5]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)[N:7]=1.[NH2:25][C@@H:26]([CH2:30][OH:31])[CH:27]([CH3:29])[CH3:28].CS(C)=O.C(N(C(C)C)CC)(C)C>O>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([N:11]2[CH2:12][CH2:13][N:8]([C:6]3[N:7]=[C:2]([NH:25][C@H:26]([CH:27]([CH3:29])[CH3:28])[CH2:30][OH:31])[C:3]4[S@:23](=[O:24])[CH2:22][CH2:21][C:4]=4[N:5]=3)[CH2:9][CH2:10]2)=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 6950587D-ValinolHCID 86645100(R)-4-chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine-5-oxide

Product 1

HCID 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-olYield 178.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Charge (R)-4-Chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine-5-oxide (0.10 g), D-valinol (46.8 mg,), and DMSO (2 mL) to a 3 neck round bottom flask with temp. probe, nitrogen inlet and stir bar. Charge diisopropylethylamine (0.1 mL) and heat the mixture to 80° C. with stirring for 2 h. Cool the mixture to ambient temperature and charge water slowly (3-5 mL) which precipitates the product as an off-white solid. Filter the solid and rinse it with water. Dry the solid for 12 h at 50° C. under vacuum providing (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 (0.21 g, 92% yld.) as a off-white solid. Recrystallize from IPA/H2O (15 vols/0.5 vols) to give material of >99% purity. 1H NMR (400 MHz, CDCl3) δ 7.16-7.26 (m, 2H), 7.00 (bs, 1H), 6.80-6.90 (m, 2H), 4.02-4.12 (m, 1H), 3.90-4.00 (m, 4H), 3.68-3.85 (m, 3H), 3.55-3.65 (m, 1H), 3.35-3.45 (m, 1H), 3.12-3.20 (m, 4H), 2.94-3.08 (m, 2H), 1.92-2.06 (m, 1H), 0.95 (d, J=6.5 Hz, 3H), 0.90 (d, J=6.5 Hz, 3H); 13C NMR (400 MHz, CDCl3) δ 174.6, 163.1, 160.4, 150.1, 129.4, 125.3, 118.0, 107.6, 63.9, 58.6, 49.6, 44.1, 33.0, 29.7, 20.2, 19.8 (5 signals missing due to overlap); LCMS (ESI) for C21H29ClN5O2S (M+H)+: calcd. 450.2, obsvd. 450.1.

Workup

  1. stirringwith stirring for 2 h
  2. customprecipitates the product as an off-white solid
  3. filtrationFilter the solid
  4. washrinse it with water
  5. customDry the solid for 12 h at 50° C. under vacuum

Sources & evidence

ORD record
ord-14d51a3e03fa4afda08ae54f5c2e00c1
Source dataset
uspto-grants-2014_02
Patent number
US08653282B2

Linked notes

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