2-Bromo-4-chloro-1,3-thiazole → 3-(6-(4-(4-Chlorothiazol-2-yl)-4-oxobutyl)-1,3-dimethyl-2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-5-yl)benzonitrile

HRID 2201213Notes

Reaction equation

HRID 2201213 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:9]2[N:10]([CH2:22][CH2:23][CH2:24][C:25](N(OC)C)=[O:26])[CH:11]=[C:12]3[C:17]=2[C:16](=[O:18])[N:15]([CH3:19])[C:14](=[O:20])[N:13]3[CH3:21])[CH:6]=[CH:7][CH:8]=1)#[N:2].Br[C:32]1[S:33][CH:34]=[C:35]([Cl:37])[N:36]=1>C1COCC1>[Cl:37][C:35]1[N:36]=[C:32]([C:25](=[O:26])[CH2:24][CH2:23][CH2:22][N:10]2[C:9]([C:5]3[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=3)[C:1]#[N:2])=[C:17]3[C:12]([N:13]([CH3:21])[C:14](=[O:20])[N:15]([CH3:19])[C:16]3=[O:18])=[CH:11]2)[S:33][CH:34]=1

Participants

4

Reactant 2

HCID 151419642-Bromo-4-chloro-1,3-thiazole2×HCID 867234524-(5-(3-Cyanophenyl)-1,3-dimethyl-2,4-dioxo-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)-N-methoxy-N-methylbutanamide

Product 1

HCID 867234533-(6-(4-(4-Chlorothiazol-2-yl)-4-oxobutyl)-1,3-dimethyl-2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-5-yl)benzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

Isopropylmagnesium chloride lithium chloride complex solution (1.3 M in THF, 2.067 ml, 2.69 mmol) was added dropwise to a solution of 4-(5-(3-cyanophenyl)-1,3-dimethyl-2,4-dioxo-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)-N-methoxy-N-methylbutanamide (1 g, 2.442 mmol) and 2-bromo-4-chlorothiazole (Intermediate Q, step 2) (0.533 g, 2.69 mmol) in THF (24.42 mL) at 0° C. The mixture was stirred at 0° C. for 30 minutes. A further portion of isopropylmagnesium chloride lithium chloride complex solution (1.3 M in THF, 2.067 ml, 2.69 mmol) was added at 0° C. and the mixture was stirred for a further 30 minutes at 0° C. The reaction was quenched with saturated NH4Cl(aq) (20 mL) and extracted with DCM (3×20 mL). The combined organic extracts were washed with saturated NaHCO3(aq) (10 mL), dried over magnesium sulfate and evaporated under reduced pressure. Trituration with methanol afforded the title compound.

Workup

  1. stirringthe mixture was stirred for a further 30 minutes at 0° C
  2. customThe reaction was quenched with saturated NH4Cl(aq) (20 mL)
  3. extractionextracted with DCM (3×20 mL)
  4. washThe combined organic extracts were washed with saturated NaHCO3(aq) (10 mL)
  5. dry with materialdried over magnesium sulfate
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-fc0eeac572a84a60a83bbd601e0f002a
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

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