1-Hydroxybenzotriazole → HCID 25177083, compound

HRID 1811752Notes

Reaction equation

HRID 1811752 reaction equation
O[N:2]1[C:6]2C=CC=C[C:5]=2N=N1.Cl.C([N:14]=C=NCCCN(C)C)C.C(N(C(C)C)CC)(C)C.F[C:33](F)(F)[C:34]([OH:36])=O.FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[NH2:53][C:54]1[N:59]=[C:58]([C:60]2[C:61]([CH3:70])=[CH:62][C:63]([CH3:69])=[C:64]([CH:68]=2)[C:65]([OH:67])=O)[CH:57]=[C:56]([S:71][CH2:72][CH2:73][NH:74]C(=O)C(N)CCN)[N:55]=1>O1CCCC1.C(OCC)(=O)C>[NH2:53][C:54]1[N:55]=[C:56]2[CH:57]=[C:58]([C:60]3[CH:68]=[C:64]([C:65](=[O:67])[NH:2][CH2:6][CH2:5][CH:33]([NH2:14])[C:34](=[O:36])[NH:74][CH2:73][CH2:72][S:71]2)[C:63]([CH3:69])=[CH:62][C:61]=3[CH3:70])[N:59]=1

Participants

7

Reactant 4

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

Product 1

HCID 25177083HCID 25177083, compoundYield 22.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

1-Hydroxybenzotriazole (888 mg, 6.57 mmol), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (2.5 g, 13.15 mmol), and diisopropylethylamine (11.5 ml, 65.74 mmol) were dissolved in tetrahydrofuran (500 ml). A tetrahydrofuran (160 ml) solution of 5-{2-amino-6-[2-(2,4-diaminobutyrylamino)ethylsulfanyl]pyrimidin-4-yl}-2,4-dimethylbenzoic acid tri(trifluoroacetate) (1.0 g, 1.31 mmol) obtained in Step 3 above was dropwise added to the above solution over 30 minutes. The resulting mixture was stirred for four hours. The reaction solution was diluted with ethyl acetate (2 l), and sequentially washed with a saturated aqueous sodium bicarbonate solution (100 ml) and a saturated aqueous sodium chloride solution (100 ml). 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 silica gel column chromatography (developing solution: dichloromethane:methanol=10:1) to yield 4,12-diamino-18,20-dimethyl-7-thia-3,5,10,15-tetraazatricyclo[15.3.1.12,6]docosa-1(20),2(22),3,5,17(21),18-hexaene-11,16-dione (Compound 73) (119 mg) as a white solid material.

Workup

  1. washsequentially washed with a saturated aqueous sodium bicarbonate solution (100 ml)
  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 silica gel column chromatography (developing solution: dichloromethane:methanol=10:1)

Sources & evidence

ORD record
ord-50323efd8920439f8068a687b4920808
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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