Diisopropylethylamine → HCID 10322214, compound

HRID 1725581Notes

Reaction equation

HRID 1725581 reaction equation
Cl[CH2:2][CH2:3][N:4]1[C:9](=[O:10])[C:8]2[C:11]3[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][C:12]=3[S:13][C:7]=2[N:6]=[CH:5]1.[N:19]1([C:25]2[C:29]3[CH:30]=[C:31]([CH3:34])[CH:32]=[CH:33][C:28]=3[O:27][N:26]=2)[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.C(N(C(C)C)CC)(C)C.[Br-].[Na+]>CN1CCCC1=O>[CH3:18][N:15]1[CH2:16][CH2:17][C:11]2[C:8]3[C:9](=[O:10])[N:4]([CH2:3][CH2:2][N:22]4[CH2:23][CH2:24][N:19]([C:25]5[C:29]6[CH:30]=[C:31]([CH3:34])[CH:32]=[CH:33][C:28]=6[O:27][N:26]=5)[CH2:20][CH2:21]4)[CH:5]=[N:6][C:7]=3[S:13][C:12]=2[CH2:14]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 253881Sodium BromideHCID 11243073HCID 11243073, compoundHCID 53938946HCID 53938946, compound

Product 1

HCID 10322214HCID 10322214, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

3-(2-Chloroethyl)-7-methyl-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-one (2.5 g, 8.81 mol; preparation: Example A3) was stirred together with 3-piperazin-1-yl-5-methyl-1,2-benzisoxazole (2.49 g, 11.45 mmol), diisopropylethylamine (15.4 ml, 88.1 mmol), sodium bromide (4.53 g, 44.05 mmol) and N-methyl-2-pyrrolidone (40 ml) at 70° C. for 4 days. After cooling, N-methyl-2-pyrrolidone and excess diisopropylethylamine were removed under high vacuum, the residue was added to water, the aqueous phase was extracted several times with ethyl acetate, and the organic phases were washed with water, dried over magnesium sulfate and concentrated in vacuo. The very impure crude product was chromatographed on silica gel (eluent: methylene chloride with slowly increasing methanol content (0-50%)). This resulted in 0.9 g of 7-methyl-3-{2-[4-(5-methyl-1,2-benzisoxazol-3-yl)piperazin-1-yl]ethyl}-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno-[2,3-d]pyrimidin-4(3H)-one (yield: 22%) being obtained as a solid product which was converted into the corresponding dihydrochloride with ethereal hydrochloric acid.

Workup

  1. temperatureAfter cooling
  2. customN-methyl-2-pyrrolidone and excess diisopropylethylamine were removed under high vacuum
  3. additionthe residue was added to water
  4. extractionthe aqueous phase was extracted several times with ethyl acetate
  5. washthe organic phases were washed with water
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe very impure crude product was chromatographed on silica gel (eluent

Sources & evidence

ORD record
ord-b5f3c4c37a1e4f9bbccccea0111f25bd
Source dataset
uspto-grants-2009_02
Patent number
US07491729B2

Reaction notes

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