Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → HCID 90386162, compound

HRID 2170201Notes

Reaction equation

HRID 2170201 reaction equation
[CH2:1]([NH:8][C:9]1[C:14]2=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:16]=[CH:17][N:13]2[N:12]=[C:11]([C:24]2[CH:25]=[N:26][CH:27]=[C:28]([CH:32]=2)[C:29]([OH:31])=O)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:57][CH:58]([CH2:63][S:64](=[O:67])(=[O:66])[NH2:65])[C:59]([O:61][CH3:62])=[O:60]>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH2:1]([NH:8][C:9]1[C:14]2=[C:15]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:16]=[CH:17][N:13]2[N:12]=[C:11]([C:24]2[CH:25]=[N:26][CH:27]=[C:28]([CH:32]=2)[C:29]([NH:57][CH:58]([CH2:63][S:64](=[O:67])(=[O:66])[NH2:65])[C:59]([O:61][CH3:62])=[O:60])=[O:31])[N:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 78323978HCID 78323978, compoundHCID 90386456HCID 90386456, compound

Product 1

HCID 90386162HCID 90386162, compoundYield 28.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-(4-(benzylamino)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)nicotinic acid (50.0 mg, 0.119 mmol) in DMF (1 mL) was added DMAP (22.0 mg, 0.178 mmol) followed by HATU (68.0 mg, 0.178 mmol) and the reaction mixture stirred for 10 minutes at room temperature. Methyl 2-amino-3-sulfamoylpropanoate (10.8 mg, 0.0590 mmol) was added and the reaction mixture stirred at room temperature for 14 h. The reaction mixture was concentrated under reduced pressure and water (10 mL) was added to the resulting residue and the solution extracted with DCM (2×25 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (Condition B-102 as described in general methods) to obtain (methyl 2-(5-(4-(benzylamino)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)nicotinamido)-3-sulfamoylpropanoate (10.0 mg, 27.6%). LCMS Condition B-19: retention time 2.11 min, [M+1]=586.1. HPLC Condition B-30: retention time 11.20 min, Purity 98.0%. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.65 (d, J=6.3 Hz, 2H), 3.71 (s, 3H), 4.84 (d, J=5.8 Hz, 2H), 4.93 (d, J=7.1 Hz, 1H), 6.72 (t, J=5.6 Hz, 1H), 6.83 (d, J=2.8 Hz, 1H), 7.08 (br s, 2H), 7.21-7.29 (m, 1H), 7.31-7.42 (m, 5H), 7.44-7.52 (m, 2H), 7.53-7.57 (m, 2H), 7.93 (d, J=2.8 Hz, 1H), 8.95 (t, J=2.1 Hz, 1H), 9.09 (d, J=2.1 Hz, 1H), 9.44 (d, J=7.8 Hz, 1H), 9.50 (d, J=2.1 Hz, 1H).

Workup

  1. stirringthe reaction mixture stirred at room temperature for 14 h
  2. concentrationThe reaction mixture was concentrated under reduced pressure and water (10 mL)
  3. additionwas added to the resulting residue
  4. extractionthe solution extracted with DCM (2×25 mL)
  5. dry with materialThe combined organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by preparative HPLC (Condition B-102 as described in general methods)

Sources & evidence

ORD record
ord-b6ee03afb6e14aad81ab97153cff99db
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

Loading…