Dichloromethane → HCID 71471826, compound

HRID 1475524Notes

Reaction equation

HRID 1475524 reaction equation
C(OC([N:8]1[CH2:13][C@H:12]([CH2:14][O:15][CH3:16])[N:11]([CH2:17][C:18]([N:20]2[C:24]3=[N:25][C:26]([CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[CH:27][CH:28]=[C:23]3[C:22]([CH3:37])([CH3:36])[CH2:21]2)=[O:19])[CH2:10][C@H:9]1[CH3:38])=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)[Cl:47]>>[ClH:47].[CH2:29]([C:26]1[N:25]=[C:24]2[N:20]([C:18](=[O:19])[CH2:17][N:11]3[CH2:10][C@@H:9]([CH3:38])[NH:8][CH2:13][C@@H:12]3[CH2:14][O:15][CH3:16])[CH2:21][C:22]([CH3:36])([CH3:37])[C:23]2=[CH:28][CH:27]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 70981722HCID 70981722, compound

Product 1

HCID 71471826HCID 71471826, compound

Procedure

(2R,5R)-4-[2-(6-Benzyl-3,3-dimethyl-2,3-dihydro-pyrrolo[2,3-b]pyridin-1-yl)-2-oxo-ethyl]-5-methoxymethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (200 mg, 0.38 mmol) was dissolved in DCM (10 mL) and placed under a nitrogen atmosphere. TFA (2 mL) was added to the reaction which was stirred at room temperature for 40 minutes. The reaction was concentrated in vacuo. The residue was partitioned between DCM (100 mL) and aqueous sodium hydrogen carbonate (100 mL). The layers were separated and the aqueous layer was extracted with DCM (2×100 mL). The organic extracts were dried over magnesium sulfate, filtered and concentrated. Chromatography: (silica; 30 g packed in DCM and eluted with 5% MeOH in DCM-5-10% MeOH:DCM:0.5% NH4OH).gave product. This material was dissolved in EtOAc and the solution treated with 2M HCl in Et2O and concentrated in vacuo giving a white solid which was dried in an oven at 40° C. overnight giving the title compound (132 mg). 1H NMR (Me-d3-OD): 7.60 (1H, s), 7.33 (4H, s), 7.24 (1H, s), 7.03 (1H, s), 4.76 (1H, d), 4.67-4.54 (1H, m), 4.10 (2H, d), 3.84 (3H, s), 3.53 (6H, s), 3.26 (1H, d), 3.20 (3H, s), 1.38 (9H, s). MS: [M+H]+=423.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customThe residue was partitioned between DCM (100 mL) and aqueous sodium hydrogen carbonate (100 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with DCM (2×100 mL)
  5. dry with materialThe organic extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washChromatography: (silica; 30 g packed in DCM and eluted with 5% MeOH in DCM-5-10% MeOH:DCM:0.5% NH4OH)
  9. dissolutionThis material was dissolved in EtOAc
  10. additionthe solution treated with 2M HCl in Et2O
  11. concentrationconcentrated in vacuo
  12. customgiving a white solid which
  13. customwas dried in an oven at 40° C. overnight

Sources & evidence

ORD record
ord-a9b2b5af227c4ed79aabd1d83fba100b
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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