Ammonia → HCID 25129212, compound

HRID 1691485Notes

Reaction equation

HRID 1691485 reaction equation
[CH3:1][C:2]([C:7]1[C:12]2[N:13]([S:26]([C:29]3[CH:34]=[CH:33][C:32]([O:35][C:36]([F:39])([F:38])[F:37])=[CH:31][CH:30]=3)(=[O:28])=[O:27])[CH2:14][C:15]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[N:18][C:16]=3[NH:17][C:11]=2[CH:10]=[CH:9][CH:8]=1)([CH3:6])[C:3](O)=[O:4].C[N:41](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.N>CN(C=O)C.O>[CH3:1][C:2]([C:7]1[C:12]2[N:13]([S:26]([C:29]3[CH:34]=[CH:33][C:32]([O:35][C:36]([F:37])([F:38])[F:39])=[CH:31][CH:30]=3)(=[O:27])=[O:28])[CH2:14][C:15]3[CH:21]=[CH:20][C:19]([C:22]([F:24])([F:25])[F:23])=[N:18][C:16]=3[NH:17][C:11]=2[CH:10]=[CH:9][CH:8]=1)([CH3:6])[C:3]([NH2:41])=[O:4]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59618661HCID 59618661, compound

Product 1

HCID 25129212HCID 25129212, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of the product of Example 435 (217 mg, 0.4 mmol) in DMF (10 mL) was added HATU (169 mg, 0.4 mmol), Hunig's base (0.1 ml, 0.4 mmol) and NH3 (0.5 M in dioxane) (2.2 mL, 0.7 mmol). The resulting solution was stirred at rt overnight, diluted with H2O, and extracted with EtOAc(3×50 mL). The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give an oil which was purified by flash chromatography (0-7% MeOH/CH2Cl2) to give the title compound as a racemic mixture. The racemic mixture was separated by HPLC on a chiralcel OD column with 20% MeOH/CO2 as the mobile phase. The faster eluting enantiomer (E1) has a retention time of 4.0 minutes, while the slower enantiomer (E2) has a retention time of 4.6 minutes. E1: 1H NMR (500 MHz, (CD3)2CO): δ 8.11 (s, 1H), 7.73 (d, J=7.5 Hz, 1H), 7.31-7.35 (m, 3H), 7.28 (dd, J=1.5, 7.5 Hz, 1H), 7.18 (dd, J=1.5, 7.5 Hz, 1H), 7.13 (d, J=7.5 Hz, 1H), 7.09 (d, J=7.5 Hz, 2H), 6.55 (s, 1H), 6.31 (s, 1H), 5.11 (d, J=17.5 Hz, 1H), 4.81 (d, J=17.5 Hz, 1H), 1.85 (s, 3H), 1.74 (s, 3H). LCMS: m/e 587.08 (M+H)+.

Workup

  1. extractionextracted with EtOAc(3×50 mL)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give an oil which
  7. customwas purified by flash chromatography (0-7% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-bfe94274b7a94d2d9a578cf2cfeec91b
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

Loading…