Phosphoric Acid → 5-[(5S*,9R*)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-ylmethyl]-thiophene-3-carboxylic acid methyl ester

HRID 489252Notes

Reaction equation

HRID 489252 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[C@:13]3([N:17]([CH3:18])[C:16](=[O:19])[N:15]([C:20]4[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=4)[C:14]3=[O:28])[CH2:12][N:11]([CH2:29][C:30]3[S:34][CH:33]=[C:32]([C:35]([OH:37])=[O:36])[CH:31]=3)[CH2:10]2)=[CH:5][CH:4]=1)#[N:2].[CH3:38][Si](C=[N+]=[N-])(C)C.OP(O)(O)=O>C(Cl)Cl.CO.O.CO>[CH3:38][O:36][C:35]([C:32]1[CH:31]=[C:30]([CH2:29][N:11]2[CH2:10][C@@H:9]([C:6]3[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=3)[C@:13]3([N:17]([CH3:18])[C:16](=[O:19])[N:15]([C:20]4[CH:21]=[C:22]([Cl:27])[CH:23]=[C:24]([Cl:26])[CH:25]=4)[C:14]3=[O:28])[CH2:12]2)[S:34][CH:33]=1)=[O:37]

Participants

7

Reactant 3

HCID 1004Phosphoric Acid2×HCID 167693TrimethylsilyldiazomethaneHCID 11635371Bms-587101

Product 1

HCID 510719905-[(5S*,9R*)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-ylmethyl]-thiophene-3-carboxylic acid methyl ester

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolvent2×HCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of 5-[(5S*,9R*)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-ylmethyl]-thiophene-3-carboxylic acid (example 37) (0.150 g, 0.27 mmol) in DCM/MeOH (5:1 mL) was added trimethylsilyldiazomethane (2.0 M solution in hexane, 0.33 mL, 0.67 mmol) over a period of three minutes at RT. The reaction mixture was stirred at RT for twenty minutes, quenched by the slow addition of acetic acid (approximatly ten drops) and partitioned between DCM (20 mL) and saturated aqueous sodium bicarbonate (15 mL). The DCM layer was washed with brine (20 mL), dried over sodium sulfate and concentrated to yield a thick oil. LC retention time=3.34 min. Column used: YMC S5 combiscreen ODS 4.6×50 mm (4 min. gradient); Solvent A=10% MeOH, 90% H2O and 0.2% H3PO4; solvent B=90% MeOH, 10% H2O, 0.2% H3PO4.

Workup

  1. customquenched by the slow addition of acetic acid (approximatly ten drops) and
  2. custompartitioned between DCM (20 mL) and saturated aqueous sodium bicarbonate (15 mL)
  3. washThe DCM layer was washed with brine (20 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customto yield a thick oil
  7. customYMC S5 combiscreen ODS 4.6×50 mm (4 min. gradient)

Sources & evidence

ORD record
ord-37985d1a75034c7bb3435d4887c4ec4a
Source dataset
uspto-grants-2005_12
Patent number
US06977267B2

Reaction notes

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