Ammonium Chloride → HCID 118071144, compound

HRID 920847Notes

Reaction equation

HRID 920847 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([N:12]2[CH:17]([CH2:18][OH:19])[CH2:16][N:15]3[N:20]=[C:21]([I:26])[C:22]([C:23](O)=[O:24])=[C:14]3[CH2:13]2)=[O:11])=[CH:5][CH:4]=1)#[N:2].C[N:28](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[Cl-].[NH4+]>CN(C=O)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]([N:12]2[CH:17]([CH2:18][OH:19])[CH2:16][N:15]3[N:20]=[C:21]([I:26])[C:22]([C:23]([NH2:28])=[O:24])=[C:14]3[CH2:13]2)=[O:11])=[CH:7][CH:8]=1)#[N:2]

Participants

6

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 118062278HCID 118062278, compound

Product 1

HCID 118071144HCID 118071144, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of Intermediate 351F (0.12 g, 0.257 mmol) in dry DMF (3 mL) was added HATU (0.195 g, 0.512 mmol), diisopropylethylamine (224 μL, 1.128 mmol) and ammonium chloride (0.0687 g, 1.128 mmol) and the reaction mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated completely to dryness and the crude was partitioned between ethyl acetate and water. The organic layer was separated, washed with brine, dried over Na2SO4, filtered and the filtrate concentrated. The crude product was purified by silica gel chromatography (12 g REDISEP® column, eluting with 3-5% methanol in chloroform). Fractions containing the product were combined to afford Intermediate 351G (0.08 g, 67%) as an off-white solid. MS(ES): m/z=467 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 9.29 (s, 1H), 7.69-7.74 (m, 2H), 7.63-7.69 (m, 2H), 7.37-7.48 (m, 1H), 6.93 (br. s., 1H), 5.22 (d, J=18.07 Hz, 1H), 5.13 (t, J=5.27 Hz, 1H), 4.72 (d, J=4.52 Hz, 1H), 4.51 (d, J=18.57 Hz, 1H), 4.31-4.38 (m, 1H), 4.20-4.28 (m, 1H), 3.43 (t, J=6.02 Hz, 2H).

Workup

  1. concentrationThe reaction mixture was concentrated completely to dryness
  2. customthe crude was partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated
  8. customThe crude product was purified by silica gel chromatography (12 g REDISEP® column, eluting with 3-5% methanol in chloroform)
  9. additionFractions containing the product

Sources & evidence

ORD record
ord-68365b8fe27d4c968ecf3439118a4d81
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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