HCID 86695117, compound → HCID 68115555, compound

HRID 1504094Notes

Reaction equation

HRID 1504094 reaction equation
[CH3:1][N:2]([CH:10]1[CH2:15][CH2:14][CH:13]([O:16][C:17]2[C:28]3[C:27]4[C@@H:26]([CH2:29][CH:30]=[O:31])[CH2:25][CH2:24][C:23]=4[S:22][C:21]=3[N:20]=[CH:19][N:18]=2)[CH2:12][CH2:11]1)[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].[CH3:32][Mg+].[Br-]>C1COCC1>[OH:31][C@H:30]([CH3:32])[CH2:29][C@H:26]1[CH2:25][CH2:24][C:23]2[S:22][C:21]3[N:20]=[CH:19][N:18]=[C:17]([O:16][CH:13]4[CH2:14][CH2:15][CH:10]([N:2]([CH3:1])[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:6])[CH3:7])[CH2:11][CH2:12]4)[C:28]=3[C:27]1=2.[OH:31][C@@H:30]([CH3:32])[CH2:29][C@H:26]1[CH2:25][CH2:24][C:23]2[S:22][C:21]3[N:20]=[CH:19][N:18]=[C:17]([O:16][CH:13]4[CH2:14][CH2:15][CH:10]([N:2]([CH3:1])[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:6])[CH3:7])[CH2:11][CH2:12]4)[C:28]=3[C:27]1=2

Participants

5

Reactant 2

HCID 86695117HCID 86695117, compoundHCID 178418689HCID 178418689, compound

Product 2

HCID 68115555HCID 68115555, compoundYield 33%HCID 68115569HCID 68115569, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A 50-mL round-bottom flask containing a solution of tert-butyl N-methyl-N-(4-[[(3R)-3-(2-oxoethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)carbamate (500 mg, 1.12 mmol, 1.00 equiv) in anhydrous THF (20 mL) was cooled down to 0° C. under nitrogen. Then CH3MgBr (1 M in THF, 3.36 mL) was added dropwise via syringe and the resulting solution was stirred for 2 h at 0° C. The reaction was then quenched with saturated aqueous NH4Cl and extracted with 3×50 mL of ethyl acetate. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated under reduced pressure. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:2) to give the desired tert-butyl N-(4-[[(3R)-3-[(2R)-2-hydroxypropyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2 (6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (192.1, 170 mg, 33%) as a colorless oil and tert-butyl N-(4-[[(3R)-3-[(2S)-2-hydroxypropyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (130 mg, 25%) as a colorless oil, respectively.

Workup

  1. customThe reaction was then quenched with saturated aqueous NH4Cl
  2. extractionextracted with 3×50 mL of ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-82431545682f4179923d778ad40d1b74
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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