Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → HCID 87561180, compound

HRID 333353Notes

Reaction equation

HRID 333353 reaction equation
[Cl:1][C:2](=[CH2:12])[CH2:3][C:4]1([C:9]([OH:11])=O)[CH2:8][CH2:7][CH2:6][CH2:5]1.OC(C(F)(F)F)=O.[NH2:20][C@@H:21]([CH2:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[CH:35][CH:34]=1)[C:22]([N:24]([CH2:26][C:27]1[O:28][CH:29]=[CH:30][CH:31]=1)[CH3:25])=[O:23].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CN(C=O)C>[C:36]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:35]=[CH:34][C:33]([CH2:32][C@H:21]([NH:20][C:9]([C:4]2([CH2:3][C:2]([Cl:1])=[CH2:12])[CH2:5][CH2:6][CH2:7][CH2:8]2)=[O:11])[C:22]([N:24]([CH2:26][C:27]2[O:28][CH:29]=[CH:30][CH:31]=2)[CH3:25])=[O:23])=[CH:38][CH:37]=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 86665070HCID 86665070, compoundHCID 131732001HCID 131732001, compound

Product 1

HCID 87561180HCID 87561180, compoundYield 71.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(2-chloroallyl)cyclopentanecarboxylic acid (80 mg, 0.42 mmol) in CH2Cl2 (3 mL) and DMF (3 mL) with (S)-2-amino-3-(biphenyl-4-yl)-N-(furan-2-ylmethyl)-N-methylpropanamide TFA salt (199 mg, 0.59 mmol) was added TEA (0.41 mL, 2.97 mmol) and HATU (161 mg, 0.42 mmol). The mixture was stirred at room temperature for 1 hour. The mixture was quenched with aq. NaHCO3 and extracted with EtOAc. The organic layer was washed with water (seven times), brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography using 10% EtOAc/heptane to 100% EtOAc/heptane to give (S)—N-(3-(biphenyl-4-yl)-1-((furan-2-ylmethyl)(methyl)amino)-1-oxopropan-2-yl)-1-(2-chloroallyl)cyclopentanecarboxamide (151 mg). HPLC retention time=1.89 minutes (condition B); MS (m+1)=505.3. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.61-1.80 (m, 12H), 1.96-2.19 (m, 4H), 2.54-2.83 (m, 6H), 2.74 (s, 3H, major rotamer), 2.95 (s, 3H, minor rotamer), 2.01-3.13 (m, 2H), 4.23 (d, J=16.7 Hz, 1H, minor rotamer), 4.28 (d, J=15.2 Hz, 1H, major rotamer), 4.44 (d, J=16.7 Hz, 1H, minor rotamer), 4.77 (d, J=15.2 Hz, 1H, major rotamer), 5.06 (s, 1H, minor rotamer), 5.12 (d, J=1.3 Hz, 1H, major rotamer), 5.15 (d, J=1.3 Hz, 1H, minor rotamer), 5.19 (d, J=1.3 Hz, 1H, major rotamer), 5.17-5.28 (m, 1H, major rotamer), 5.39 (q, J=7.2 Hz, 1H, minor rotamer), 6.17 (d, J=2.8 Hz, 1H, minor rotamer), 6.24 (d, J=3.3 Hz, 1H, major rotamer), 6.30 (dd, J=3.3, 1.8 Hz, 1H, minor rotamer), 6.37 (dd, J=3.2, 1.9 Hz, 1H, major rotamer), 6.57 (d, J=8.1 Hz, 1H, minor rotamer), 6.68 (d, J=7.8 Hz, 1H, major rotamer), 7.21-7.65 (m, 18H).

Workup

  1. customThe mixture was quenched with aq. NaHCO3
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with water (seven times), brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-2f70dd2f1d5e4e94bfcab1910a81ec9f
Source dataset
uspto-grants-2014_11
Patent number
US08877815B2

Reaction notes

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