Ammonium Chloride → HCID 90370135, compound

HRID 2176053Notes

Reaction equation

HRID 2176053 reaction equation
[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([C:14]3[O:15][C:16](=[O:27])[C:17]4[C:22]5[CH2:23][CH2:24][CH2:25][CH2:26][C:21]=5[S:20][C:18]=4[N:19]=3)[CH:11]=[CH:12][CH:13]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH2:28]([N:30]([CH2:38][CH3:39])[C:31]1[N:36]=[CH:35][C:34]([NH2:37])=[CH:33][N:32]=1)[CH3:29].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[Cl-:50].[NH4+]>C1COCC1>[ClH:50].[ClH:50].[CH2:38]([N:30]([CH2:28][CH3:29])[C:31]1[N:36]=[CH:35][C:34]([NH:37][C:16]([C:17]2[C:22]3[CH2:23][CH2:24][CH2:25][CH2:26][C:21]=3[S:20][C:18]=2[NH:19][C:14](=[O:15])[C:10]2[CH:11]=[CH:12][CH:13]=[C:8]([CH2:7][N:1]3[CH2:2][CH2:3][O:4][CH2:5][CH2:6]3)[CH:9]=2)=[O:27])=[CH:33][N:32]=1)[CH3:39]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 45088895HCID 45088895, compoundHCID 90370056HCID 90370056, compound

Product 1

HCID 90370135HCID 90370135, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 350 mg of 2-[3-(morpholin-4-ylmethyl)phenyl]-5,6,7,8-tetrahydro-4H-[1]benzothieno[2,3-d][1,3]oxazin-4-one, 150 mg of 2-N,2-N-diethylpyrimidine-2,5-diamine and 5.0 mL of THF was added dropwise 1.0 mL of lithium hexamethyldisilazide (1.0 M in THF) under ice cooling, followed by stirring for 1 hour at the same temperature. A saturated aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (methanol/chloroform). Ethyl acetate and 0.5 mL of 4.0 M hydrogen chloride/ethyl acetate solution were sequentially added to the residue, followed by stirring for 30 minutes at room temperature. The insoluble material was collected by filtration, thereby obtaining 174 mg of N-[2-(diethylamino)pyrimidin-5-yl]-2-{[3-(morpholin-4-ylmethyl)benzoyl]amino}-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide dihydrochloride.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was removed under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (methanol/chloroform)
  6. additionEthyl acetate and 0.5 mL of 4.0 M hydrogen chloride/ethyl acetate solution were sequentially added to the residue
  7. stirringby stirring for 30 minutes at room temperature
  8. filtrationThe insoluble material was collected by filtration

Sources & evidence

ORD record
ord-4dfcff5658184964b9df4acefe74cdbc
Source dataset
uspto-grants-2015_06
Patent number
US09062032B2

Reaction notes

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