Ammonium Chloride → HCID 58204213, compound

HRID 1849454Notes

Reaction equation

HRID 1849454 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([C:23]5[CH:24]=[C:25]([CH2:29][C:30](O)=[O:31])[CH:26]=[CH:27][CH:28]=5)[CH:20]=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].CC[N:35](C(C)C)C(C)C.[Cl-].[NH4+].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[CH:1]([N:4]1[C:8]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([C:23]5[CH:24]=[C:25]([CH2:29][C:30]([NH2:35])=[O:31])[CH:26]=[CH:27][CH:28]=5)[CH:20]=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][CH:6]=[N:5]1)([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67050618HCID 67050618, compound

Product 1

HCID 58204213HCID 58204213, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of crude {3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-phenyl}-acetic acid (0.38 mmol) in 5 mL DMF was treated sequentially with DIPEA (0.33 mL, 1.92 mmol), ammonium chloride (164 mg, 3.1 mmol) and HATU (292 mg, 0.77 mmol). The reaction was monitored by LCMS. After complete conversion, the mixture was diluted with water and extracted with ethylacetate. The combined organics were washed with brine, dried over sodium sulfate and concentrated. The crude residue was purified by reverse phase HPLC to give 522 as a colorless solid (93 mg, 56%). LCMS: 446.1. 1H NMR (400 MHz, DMSO) δ 8.45 (d, J=8.3 Hz, 1H), 8.11 (s, 1H), 7.66 (s, 1H), 7.60 (d, J=7.8 Hz, 1H), 7.54 (dd, J=8.3, 1.8 Hz, 1H), 7.49 (s, 1H), 7.44-7.35 (m, 2H), 7.27 (d, J=7.6 Hz, 1H), 6.88 (s, 1H), 5.92-5.78 (m, 1H), 4.43 (t, J=4.9 Hz, 2H), 3.47 (overlapping m, 4H), 1.57 (d, J=6.6 Hz, 6H)

Workup

  1. extractionextracted with ethylacetate
  2. washThe combined organics were washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe crude residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-3bef8f4624604ea792e571c55bedda49
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

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