Hydrochloric Acid → HCID 76286518, compound

HRID 1050295Notes

Reaction equation

HRID 1050295 reaction equation
[C:1]([CH2:3][CH2:4][N:5]1[CH2:13][C@H:12]([OH:14])[CH2:11][C@H:6]1[C:7](OC)=O)#[N:2].Cl.O1[CH2:21][CH2:20]OCC1.C(N(CC)CC)C.[F:29][C:30]([F:41])([F:40])[C:31]1[CH:32]=[CH:33][C:34]([C:37]([OH:39])=O)=[N:35][CH:36]=1.O.O[N:44]1[C:48]2[CH:49]=[CH:50][CH:51]=C[C:47]=2[N:46]=N1.Cl.CN(C)CCCN=C=NCC>CO.ClCCl>[CH:49]1([C:48]2[N:44]=[CH:20][C:21]([O:14][C@H:12]3[CH2:13][N:5]4[CH2:4][CH2:3][CH2:1][N:2]([C:37]([C:34]5[CH:33]=[CH:32][C:31]([C:30]([F:29])([F:41])[F:40])=[CH:36][N:35]=5)=[O:39])[CH2:7][C@@H:6]4[CH2:11]3)=[N:46][CH:47]=2)[CH2:50][CH2:51]1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 109103495-(trifluoromethyl)pyridine-2-carboxylic AcidHCID 86723178HCID 86723178, compound

Product 1

HCID 76286518HCID 76286518, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of the product from Example 1, Part D (50 mg, 0.134 mmol) in anhydrous methanol (2 mL) was added 4 M HCl in 1,4-dioxane (0.334 mL, 1.335 mmol), and the resulting mixture was stirred at room temperature for 18 hours and concentrated in vacuo. The residue was dissolved in a mixture of dichloromethane (8 mL) and triethylamine (0.093 mL, 0.668 mmol), and then 5-(trifluoromethyl)picolinic acid (0.026 g, 0.134 mmol), 1-hydroxybenzotriazole hydrate (0.025 g, 0.160 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.031 g, 0.160 mmol) were added. The resulting mixture was stirred at room temperature for 16 hours, and then it was partitioned between water and ethyl acetate. The organic extract was washed successively with water and brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-4% methanol in dichloromethane to give the title compound as a waxy solid (0.042 g, 70%). 1H NMR (400 MHz, pyridine-d5) δ ppm 9.05-8.97 (m, 1H), 8.28-8.13 (m, 2H), 8.11 (dd, J=19.6, 1.4 Hz, 1H), 8.00 (dd, J=18.4, 8.2 Hz, 1H), 5.45-5.32 (m, 1H), 4.59 (dd, J=13.5, 2.2 Hz, 1H), 4.14-3.95 (m, 1H), 3.85-3.68 (m, 1H), 3.59 (dd, J=12.1, 6.0 Hz, 2H), 3.18 (ddd, J=17.4, 13.7, 9.8 Hz, 1H), 3.10-2.94 (m, 2H), 2.64-2.53 (m, 1H), 2.51-2.38 (m, 1H), 2.16-1.70 (m, 4H), 1.14-0.98 (m, 2H), 0.99-0.84 (m, 2H); MS (ESI) m/z 448 (M+H)+.

Workup

  1. concentrationconcentrated in vacuo
  2. stirringThe resulting mixture was stirred at room temperature for 16 hours
  3. customit was partitioned between water and ethyl acetate
  4. extractionThe organic extract
  5. washwas washed successively with water and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-4% methanol in dichloromethane

Sources & evidence

ORD record
ord-7bc7ab80bbd2402d822387aee4ef7933
Source dataset
uspto-grants-2016_07
Patent number
US09382258B2

Reaction notes

Loading…