Formic Acid → HCID 178464204, compound

HRID 931227Notes

Reaction equation

HRID 931227 reaction equation
Cl.Cl.[NH2:3][C:4]1[CH:5]=[CH:6][C:7]([N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([C:17]([N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)=[O:18])[CH2:12]2)=[N:8][C:9]=1[NH2:10].C(O)=O.[CH2:27]([OH:32])[C:28](F)(F)F.ClC(Cl)(Cl)C(=N)OC.[CH2:41]([NH:43][CH2:44][CH3:45])[CH3:42]>>[CH2:41]([N:43]([CH2:44][CH3:45])[C:27]([C:28]1[NH:10][C:9]2=[N:8][C:7]([N:11]3[CH2:16][CH2:15][CH2:14][C@@H:13]([C:17]([N:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)=[O:18])[CH2:12]3)=[CH:6][CH:5]=[C:4]2[N:3]=1)=[O:32])[CH3:42]

Participants

6

Reactant 5

HCID 284Formic AcidHCID 64092,2,2-TrifluoroethanolHCID 8021DiethylamineHCID 100479Methyl 2,2,2-trichloroacetimidateHCID 89854051(R)-(1-(5,6-Diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride

Product 1

HCID 178464204HCID 178464204, compound

Procedure

Into a vial containing (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (125 mg, 0.3 mmol) was added formic acid (73.5 μL, 1.7 mmol) followed by 2,2,-trifluoroethanol (1.7 mL) and methyl 2,2,2-trichloroacetimidate (47.0 μL, 0.4 mmol). The vial was sealed and stirred at room temperature for 13 min. The reaction mixture was heated to 60° C. and stirred for 3 h at that temperature. An aliquot of 0.3 mL was transferred into another vial containing diethylamine (89.1 μL, 0.9 mmol). The resulting mixture was heated to 60° C. and stirred for 16 h. The reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between water and ethyl acetate. The aqueous was further extracted with ethyl acetate. The combined organics were concentrated under reduced pressure. The residue was purified via HPLC to afford the title compound. MS (ESI+) (M+H) 399.1; HPLC retention time 1.9864 min (Method A).

Workup

  1. customThe vial was sealed
  2. temperatureThe reaction mixture was heated to 60° C.
  3. stirringstirred for 3 h at that temperature
  4. temperatureThe resulting mixture was heated to 60° C.
  5. stirringstirred for 16 h
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. customthe resulting residue was partitioned between water and ethyl acetate
  8. extractionThe aqueous was further extracted with ethyl acetate
  9. concentrationThe combined organics were concentrated under reduced pressure
  10. customThe residue was purified via HPLC

Sources & evidence

ORD record
ord-d6f2dc8418f8475fb98d409e995eb45c
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

Loading…