Water → HCID 66817508, compound

HRID 1755091Notes

Reaction equation

HRID 1755091 reaction equation
[CH:1]1([C:7]2[NH:11][C:10](=[O:12])[C:9]3([CH2:17][CH2:16][N:15]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:14][CH2:13]3)[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH3:32][C:33]1([CH3:50])[O:37][C@@H:36]([CH2:38][N:39]2[C:47]3[CH:46]=[CH:45][CH:44]=[C:43]([CH:48]=[O:49])[C:42]=3[CH:41]=[CH:40]2)[CH2:35][O:34]1.O>CN1CCCN(C)C1=O.O1CCCC1>[CH:1]1([C:7]2[NH:11][C:10](=[O:12])[C:9]3([CH2:17][CH2:16][N:15]([S:18]([CH2:21][CH:48]([C:43]4[CH:44]=[CH:45][CH:46]=[C:47]5[C:42]=4[CH:41]=[CH:40][N:39]5[CH2:38][C@H:36]4[CH2:35][O:34][C:33]([CH3:50])([CH3:32])[O:37]4)[OH:49])(=[O:20])=[O:19])[CH2:14][CH2:13]3)[N:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 962WaterHCID 2733832Lithium HexamethyldisilazideHCID 66817608HCID 66817608, compoundHCID 87166732HCID 87166732, compound

Product 1

HCID 66817508HCID 66817508, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
0 °C

Procedure

A suspension of 2-cyclohexyl-8-methanesulfonyl-1,3,8-triaza-spiro[4.5]dec-1-en-4-one (100 mg, 0.319 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.66 mL) was cooled to 0° C. A 1 M solution of lithium hexamethyldisilazide in tetrahydrofuran (0.989 ml) was then added and the mixture was stirred at room temperature for 30 minutes. After cooling again to 0° C., a solution of 1-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-indole-4-carbaldehyde (87 mg, 0.335 mmol) in tetrahydrofuran (0.4 mL) was added and the mixture was stirred at 0° C. for five hours. Water was added and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with water and then dried over sodium sulfate. After concentration, the residue was purified by silica gel column chromatography to give 2-cyclohexyl-8-{2-[1-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H indol-4-yl]-2-hydroxy-ethanesulfonyl}-1,3,8-triaza-spiro[4.5]dec-1-en-4-one (113 mg, 62%) as a pale yellow solid.

Workup

  1. temperatureAfter cooling again to 0° C.
  2. stirringthe mixture was stirred at 0° C. for five hours
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washThe organic layer was washed with water
  5. dry with materialdried over sodium sulfate
  6. concentrationAfter concentration
  7. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-553c8dc3a4e54ea38a824f509a531d58
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

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