1-Hydroxybenzotriazole → HCID 11988445, compound

HRID 1157672Notes

Reaction equation

HRID 1157672 reaction equation
[Cl:1][C:2]1[C:3]([CH3:18])=[C:4]([N:10]2[CH2:17][CH2:16][CH2:15][C@H:11]2[C:12]([OH:14])=O)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)CC)(C)C.ON1C2C=CC=CC=2N=N1.O[NH:61][C:62](=[NH:64])[CH3:63]>CN(C=O)C>[Cl:1][C:2]1[C:3]([CH3:18])=[C:4]([N:10]2[CH2:17][CH2:16][CH2:15][CH:11]2[C:12]2[O:14][N:64]=[C:62]([CH3:63])[N:61]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 68699150HCID 68699150, compoundHCID 178465666HCID 178465666, compound

Product 1

HCID 11988445HCID 11988445, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
21 °C

Procedure

To a solution of 1-(3-chloro-4-cyano-2-methylphenyl)proline (0.200 g, 0.756 mmol), TBTU (0.364 g, 1.136 mmol), diisopropylethylamine (0.458 g, 3.78 mmol) and N-hydroxybenzotriazole (0.023 g, 0.150 mmol) in DMF add N-hydroxyacetamidine (0.084 g, 1.136 mmol). Stir the solution at 21° C. for 18 h. then heat the reaction at 100° C. in a microwave for 1 h. Partition the reaction between ethyl acetate and 2N aqueous hydrochloric acid. Extract the organic phase with 2N aqueous sodium hydroxide and brine, dry over magnesium sulphate, filter and remove the solvent under reduced pressure. Purify the resulting residue by reverse phase HPLC (Princeton SPHER C-18 column, gradient of 80:20 to 5:95 [water:acetonitrile], with 0.1% acetic acid modifier)) to yield the title compound. (0.81 g, 35%) mass spectrum (m/e): 303.1 (M+Na)); 1H NMR (400 MHz, CDCl3): δ 7.35 (d, 1H), 6.99 (d, 1H), 5.11 (t, 1H), 3.88 (m, 1H), 3.16 (m, 1H), 2.56 (m, 1H), 2.39 (s, 3H), 2.31 (s, 3H), 2.30-2.15 (m. 3H), 2.06 (m, 1H).

Workup

  1. temperaturethen heat
  2. customthe reaction at 100° C. in a microwave for 1 h
  3. customPartition
  4. customthe reaction between ethyl acetate and 2N aqueous hydrochloric acid
  5. extractionExtract the organic phase with 2N aqueous sodium hydroxide and brine
  6. dry with materialdry over magnesium sulphate
  7. filtrationfilter
  8. customremove the solvent under reduced pressure
  9. customPurify the resulting residue by reverse phase HPLC (Princeton SPHER C-18 column, gradient of 80:20 to 5:95 [water:acetonitrile], with 0.1% acetic acid modifier))

Sources & evidence

ORD record
ord-05c68f24cecf478a85321c7ddd180adc
Source dataset
uspto-grants-2010_10
Patent number
US07807691B2

Reaction notes

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