Ammonium Chloride → HCID 68044431, compound

HRID 1524366Notes

Reaction equation

HRID 1524366 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:20]([NH:22][CH2:23][C:24]([F:52])([F:51])[CH2:25][CH2:26][C@@H:27]([C:48](O)=[O:49])[N:28]([S:36]([C:39]1[CH:47]=[CH:46][C:42]2[N:43]=[CH:44][S:45][C:41]=2[CH:40]=1)(=[O:38])=[O:37])[CH2:29][CH:30]1[CH2:33][C:32]([F:35])([F:34])[CH2:31]1)=[O:21])[CH:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4].O[N:54]1C2C=CC=CC=2N=N1.[Cl-].[NH4+].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C.O>[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:20]([NH:22][CH2:23][C:24]([F:51])([F:52])[CH2:25][CH2:26][C@@H:27]([C:48]([NH2:54])=[O:49])[N:28]([S:36]([C:39]1[CH:47]=[CH:46][C:42]2[N:43]=[CH:44][S:45][C:41]=2[CH:40]=1)(=[O:37])=[O:38])[CH2:29][CH:30]1[CH2:31][C:32]([F:35])([F:34])[CH2:33]1)=[O:21])[CH:7]([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[O:4]

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68044511HCID 68044511, compound

Product 1

HCID 68044431HCID 68044431, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of the material from Example 4, Step 8 (98 mg, 0.128 mmol) in 1.2 mL of DMF at 0° C. were added 1-hydroxybenzotriazole (26 mg, 0.192 mmol), ammonium chloride (14 mg, 0.256 mmol), HATU (73 mg, 0.192 mmol) and N,N-diisopropylethylamine (67 μL, 0.358 mmol). The reaction mixture was stirred at 0° C. over the week-end. It was poured into water and extracted with EtOAc (2×). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by reverse phase column using Zorbax Eclise Plus C18 RRHT 3×50 mm, 1.8 u column. Gradient: MeCN/H2O+0.1% HCO2H from 10:90 to 95:5 over 5 minutes. Flow: 1.0 mL/min. Positive ion mode. The title compound was obtained as a colorless foam. LCMS (M+1)=764. 1H NMR (Acetone-d6): δ 9.56 (s, 1H), 8.83 (d, J=12.07 Hz, 1H), 8.41-8.25 (m, 1H), 8.08 (d, J=8.22 Hz, 1H), 7.59 (s, 1H), 7.48-7.38 (m, 4H), 7.35-7.25 (m, 4H), 7.24-7.13 (m, 2H), 6.81 (s, 1H), 6.76-6.60 (m, 1H), 6.46 (d, J=8.74 Hz, 1H), 5.16-5.02 (m, 1H), 4.49-4.41 (m, 1H), 4.38-4.31 (m, 1H), 3.69-3.57 (m, 1H), 3.34 (s, 3H), 3.47-3.20 (m, 3H), 3.14-2.89 (m, 1H), 2.71-2.26 (m, 4H), 2.04-1.84 (m, 2H), 1.52-1.10 (m, 2H).

Workup

  1. extractionextracted with EtOAc (2×)
  2. washThe combined organics were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by reverse phase column

Sources & evidence

ORD record
ord-548dc1b00f7447a6a4c80b5395330a23
Source dataset
uspto-grants-2015_07
Patent number
US09079834B2

Reaction notes

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