Ammonium Chloride → HCID 67430966, compound

HRID 410636Notes

Reaction equation

HRID 410636 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:20][C:21]2[N:26]=[C:25]([O:27][CH2:28][C:29](O)=[O:30])[CH:24]=[CH:23][N:22]=2)[CH:5]=[C:6]([C:8]2[S:12][C:11]([C:13]([OH:19])([CH3:18])[C:14]([F:17])([F:16])[F:15])=[N:10][CH:9]=2)[CH:7]=1.O[N:33]1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.Cl.C(N=C=NCCCN(C)C)C.[Cl-].[NH4+]>CN(C)C=O>[CH3:1][C:2]1[CH:3]=[C:4]([NH:20][C:21]2[N:26]=[C:25]([O:27][CH2:28][C:29]([NH2:33])=[O:30])[CH:24]=[CH:23][N:22]=2)[CH:5]=[C:6]([C:8]2[S:12][C:11]([C:13]([OH:19])([CH3:18])[C:14]([F:16])([F:15])[F:17])=[N:10][CH:9]=2)[CH:7]=1

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67432651HCID 67432651, compound

Product 1

HCID 67430966HCID 67430966, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The product of Step 1 (10 mg, 0.018 mmol), N-hydroxybenzotriazole (5.4 mg, 0.035 mmol), diisopropylethylamine (31 μL, 0.18 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (6.7 mg, 0.035 mmol) were taken-up in N,N-dimethylformamide (0.5 mL). Ammonium chloride (6.6 mg, 0.12 mmol) was added in one portion, and the resulting mixture was stirred overnight at room temperature. The resulting mixture was directly purified via reverse phase HPLC (10-80% acetonitrile/water+0.05% TFA modifier). Desired fractions were combined, diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate (1×) and 10% aqueous ammonium hydroxide (1×). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo to afford 2-{[2-({3-methyl-5-[2-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1,3-thiazol-5-yl]phenyl}amino)pyrimidin-4-yl]oxy}acetamide (6 mg, 0.013 mmol, 76% yield) as a white solid. MS ESI: [M+H]+ m/z 454.1. 1H NMR (500 MHz, DMSO-d6) δ 9.55 (s, 1H), 8.25 (d, J=5.5 Hz, 1H), 8.07 (s, 1H), 7.70 (s, 1H), 7.68 (s, 1H), 7.64 (s, 1H), 7.49 (s, 1H), 7.31 (s, 1H), 7.09 (s, 1H), 6.35 (d, J=5.5 Hz, 1H), 4.76 (s, 2H), 2.32 (s, 3H), 1.76 (3H).

Workup

  1. customThe resulting mixture was directly purified via reverse phase HPLC (10-80% acetonitrile/water+0.05% TFA modifier)
  2. additiondiluted with ethyl acetate
  3. washwashed with saturated aqueous sodium bicarbonate (1×) and 10% aqueous ammonium hydroxide (1×)
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1feabb565894434ea1872ee6598ead9e
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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