HCID 86695090, compound → HCID 68115512, compound

HRID 1503925Notes

Reaction equation

HRID 1503925 reaction equation
[O:1]=[CH:2][CH2:3][C@H:4]1[CH2:15][CH2:14][C:13]2[S:12][C:11]3[N:10]=[CH:9][N:8]=[C:7]([NH:16][CH:17]4[CH2:22][CH2:21][CH:20]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:19][CH2:18]4)[C:6]=3[C:5]1=2.[CH3:31][Mg+].[Br-]>O1CCCC1>[OH:1][CH:2]([CH3:31])[CH2:3][C@H:4]1[CH2:15][CH2:14][C:13]2[S:12][C:11]3[N:10]=[CH:9][N:8]=[C:7]([NH:16][CH:17]4[CH2:18][CH2:19][CH:20]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:27])([CH3:29])[CH3:28])[CH2:21][CH2:22]4)[C:6]=3[C:5]1=2

Participants

4

Reactant 2

HCID 86695090HCID 86695090, compound2×HCID 178418689HCID 178418689, compound

Product 1

HCID 68115512HCID 68115512, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

For the preparation of the starting material compound 26.3, see Example 26. Into a 50-mL 3-necked round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, was placed a solution of tert-butyl 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]amino]cyclohexyl)carbamate (250 mg, 0.58 mmol, 1.00 equiv) in freshly distilled tetrahydrofuran (10 mL) at 0° C. under nitrogen. The CH3MgBr (1.0 M in THF, 2.9 mL, 5.0 equiv) was added at 0° C. via syringe. The resulting solution was stirred for 2 h at 0° C. and quenched with saturated aqueous NH4Cl and extracted with 3×30 mL of ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate and concentrated under reduced pressure. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5) to give the desired racemic tert-butyl N-(4-[[(3R)-3-(2-hydroxypropyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]amino]cyclohexyl)carbamate (109 mg, 42%) as a colorless oil.

Workup

  1. customInto a 50-mL 3-necked round-bottom flask, purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customat 0° C.
  4. customquenched with saturated aqueous NH4Cl
  5. extractionextracted with 3×30 mL of ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b7024170b05f4086925a7a81d948d3b6
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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