1-Hydroxybenzotriazole → HCID 25177018, compound

HRID 1811753Notes

Reaction equation

HRID 1811753 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3](O)=[O:4].FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[NH2:22][C:23]1[N:28]=[C:27]([C:29]2[C:30]([CH3:39])=[CH:31][C:32]([CH3:38])=[C:33]([CH:37]=2)[C:34]([OH:36])=O)[CH:26]=[C:25]([S:40][CH2:41][CH2:42][NH:43][C:44](=[O:50])[CH:45]([NH2:49])[CH2:46][CH2:47][NH2:48])[N:24]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[NH2:22][C:23]1[N:24]=[C:25]2[CH:26]=[C:27]([C:29]3[CH:37]=[C:33]([C:34](=[O:36])[NH:48][CH2:47][CH2:46][CH:45]([NH:49][C:3](=[O:4])[C:2]([F:7])([F:6])[F:1])[C:44](=[O:50])[NH:43][CH2:42][CH2:41][S:40]2)[C:32]([CH3:38])=[CH:31][C:30]=3[CH3:39])[N:28]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86639755HCID 86639755, compound

Product 1

HCID 25177018HCID 25177018, compoundYield 30.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-{2-Amino-6-[2-(2,4-diaminobutyrylamino)ethylsulfanyl]pyrimidin-4-yl}-2,4-dimethylbenzoic acid tri(trifluoroacetate) (60 mg, 0.079 mmol) obtained in Step 3 of Example 3-8 and 1-hydroxybenzotriazole (43 mg, 0.316 mmol) were dissolved in N,N-dimethylformamide (46 ml). 1-Ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (61 mg, 0.316 mmol) and diisopropylethylamine (8.3 μl, 0.473 mmol) were added to the solution, and stirred overnight at room temperature. The reaction solution was diluted with ethyl acetate, and then sequentially washed with a saturated aqueous sodium bicarbonate solution, water (three times), and a saturated aqueous sodium chloride solution. After the organic layer was dried over anhydrous sodium sulfate, the inorganic salt was filtered and washed with ethyl acetate. The filtrate and washing solution were combined together, and concentrated under reduced pressure. The resulting residue was purified by preparative thin layer silica gel chromatography (developing solvent: dichloromethane:methanol=10:1) to yield N-(4-amino-18,20-dimethyl-11,16-dioxo-7-thia-3,5,10,15-tetraazatricyclo[15.3.1.12,6]docosa-1(20),2(22),3,5,17(21),18-hexaen-12-yl)-2,2,2-trifluoroacetamide (Compound 75) (12 mg) as a white solid material.

Workup

  1. washsequentially washed with a saturated aqueous sodium bicarbonate solution, water (three times)
  2. dry with materialAfter the organic layer was dried over anhydrous sodium sulfate
  3. filtrationthe inorganic salt was filtered
  4. washwashed with ethyl acetate
  5. washThe filtrate and washing solution
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by preparative thin layer silica gel chromatography (developing solvent: dichloromethane:methanol=10:1)

Sources & evidence

ORD record
ord-273fb8c76b6f491faab667407736a9cc
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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