Hydrochloric Acid → HCID 68782797, compound

HRID 1968536Notes

Reaction equation

HRID 1968536 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[C@@H:14]3[CH2:15][C@@H:11]([CH:12]=[CH:13]3)[C@@H:10]2[C:16]([NH2:18])=[O:17])[C:5]([Cl:19])=[CH:4][N:3]=1.[NH2:20][C:21]1[CH:22]=[N:23][N:24]([CH2:26][C@H:27]2[CH2:31][CH2:30][CH2:29][N:28]2C(OC(C)(C)C)=O)[CH:25]=1.Cl.O1CCOCC1>CC(O)C>[Cl:19][C:5]1[C:6]([NH:8][C@@H:9]2[C@@H:14]3[CH2:15][C@@H:11]([CH:12]=[CH:13]3)[C@@H:10]2[C:16]([NH2:18])=[O:17])=[N:7][C:2]([NH:20][C:21]2[CH:22]=[N:23][N:24]([CH2:26][C@H:27]3[CH2:31][CH2:30][CH2:29][NH:28]3)[CH:25]=2)=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 57522618HCID 57522618, compoundHCID 67127464HCID 67127464, compound

Product 1

HCID 68782797HCID 68782797, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
85 °C

Procedure

(1S,2S,3R,4R)-3-(2,5-Dichloropyrimidin-4-ylamino)bicyclo[2.2.1]hept-5-ene-2-carboxamide (100 mg, 0.334 mmol) and (R)-tert-butyl 2-((4-amino-1H-pyrazol-1-yl)methyl)pyrrolidine-1-carboxylate (116 mg, 0.435 mmol) were combined with 2-propanol (2 ml) and 4N HCl in dioxane (0.084 ml, 0.334 mmol) in a sealed tube and the reaction was heated to 85° C. for 4 hours. The reaction mixture was concentrated to dryness, and the residue was treated with trifluoroacetic acid (3 mL). After stirring at room temperature for 30 minutes, the reaction mixture was again concentrated to dryness and the residue was suspended in saturated aqueous NaHCO3 (5 mL). The resulting mixture was extracted with CH2Cl2 (2×10 mL) and ethyl acetate (2×10 mL). The organic extracts were combined, dried (Na2SO4) filtered, and concentrated. The residue was purified by flash chromotography (Analogix, 4 g column, 15 mL/minutes, 0 to 20% methanol (containing 5% NH4OH)/CH2Cl2 over 25 minutes) to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.30-1.44 (m, 2H) 1.53-1.81 (m, 3H) 2.11 (d, J=8.82 Hz, 1H) 2.51-2.56 (m, 1H) 2.75-2.85 (m, 3H) 2.86-2.89 (m, 1H) 3.37-3.47 (m, 1H) 3.93-4.01 (m, 2H) 4.12 (t, J=7.12 Hz, 1H) 6.31-6.39 (m, 2H) 7.25 (s, 1H) 7.52 (s, 1H) 7.65-7.83 (m, 3H) 7.89 (s, 1H) 9.10 (s, 1H); MS (ESI(+)) m/e 429 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. additionthe residue was treated with trifluoroacetic acid (3 mL)
  3. concentrationthe reaction mixture was again concentrated to dryness
  4. extractionThe resulting mixture was extracted with CH2Cl2 (2×10 mL) and ethyl acetate (2×10 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromotography (Analogix, 4 g column, 15 mL/minutes, 0 to 20% methanol (containing 5% NH4OH)/CH2Cl2 over 25 minutes)

Sources & evidence

ORD record
ord-f5cc885dc580428282c8cc990e82bc80
Source dataset
uspto-grants-2013_04
Patent number
US08426408B2

Reaction notes

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