4-Morpholinecarbonitrile → 6-bromo-2-morpholin-4-ylthieno[3,2-d]pyrimidin-4(3H)-one

HRID 1052160Notes

Reaction equation

HRID 1052160 reaction equation
[NH2:1][C:2]1[CH:6]=[C:5]([Br:7])[S:4][C:3]=1[C:8]([O:10]C)=O.[N:12]1([C:18]#[N:19])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.Cl.C1(OC)CCCC1>>[Br:7][C:5]1[S:4][C:3]2[C:8](=[O:10])[NH:19][C:18]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[N:1][C:2]=2[CH:6]=1

Participants

4

Reactant 3

HCID 737384-MorpholinecarbonitrileHCID 20158931Methyl 3-amino-5-bromothiophene-2-carboxylateHCID 66926893hydrogen chloride CPME

Product 1

HCID 1363339126-bromo-2-morpholin-4-ylthieno[3,2-d]pyrimidin-4(3H)-one

Conditions

Temperature
110 °C

Procedure

A mixture of methyl 3-amino-5-bromothiophene-2-carboxylate (200 mg) produced in Example 1, step C, morpholine-4-carbonitrile (0.17 mL) and 4M hydrochloric acid/cyclopentylmethylether solution (3.0 mL) was stirred at 110° C. for 4 hr. The reaction system was concentrated under reduced pressure, and saturated aqueous sodium hydrogen carbonate was added to the residue. The precipitate was collected by filtration and washed with water. The obtained pale-brown solid was washed with a mixed solvent of ethyl acetate/hexane (1:1) to give the title compound (144 mg) as a pale-yellow solid.

Workup

  1. concentrationThe reaction system was concentrated under reduced pressure, and saturated aqueous sodium hydrogen carbonate
  2. additionwas added to the residue
  3. filtrationThe precipitate was collected by filtration
  4. washwashed with water
  5. washThe obtained pale-brown solid was washed with a mixed solvent of ethyl acetate/hexane (1:1)

Sources & evidence

ORD record
ord-a2ba18be24d24b98b27e4fc9b921883a
Source dataset
uspto-grants-2016_07
Patent number
US09388195B2

Reaction notes

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