Water → HCID 68417974, compound

HRID 1811764Notes

Reaction equation

HRID 1811764 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([S:8][CH2:9][CH2:10][C:11](O)=[O:12])[CH:5]=[C:4]([C:14]2[CH:19]=[C:18]([C:20](=[O:48])[NH:21][CH2:22]C3(CNC(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)COC3)[C:17]([CH3:49])=[CH:16][C:15]=2[CH3:50])[N:3]=1.C(N([CH:57]([CH3:59])[CH3:58])CC)(C)C.F[P-](F)(F)(F)(F)F.[N:67]1(OC(N(C)C)=[N+](C)C)[C:71]2N=CC=C[C:70]=2N=N1.[OH2:84]>CN(C)C=O>[NH2:1][C:2]1[N:7]=[C:6]2[CH:5]=[C:4]([C:14]3[CH:19]=[C:18]([C:20](=[O:48])[NH:21][CH2:22][CH:70]([CH:57]4[CH2:58][O:84][CH2:59]4)[CH2:71][NH:67][C:11](=[O:12])[CH2:10][CH2:9][S:8]2)[C:17]([CH3:49])=[CH:16][C:15]=3[CH3:50])[N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59224702HCID 59224702, compound

Product 1

HCID 68417974HCID 68417974, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

3-{2-amino-6-[2,4-dimethyl-5-({3-[(tritylamino)methyl]oxetan-3-ylmethyl}carbamoyl)phenyl]pyrimidin-4-ylsulfanyl}propanoic acid (36 mg, 0.059 mmol) obtained in Step 3 above. After confirming that the clear colorless solution changed to yellow, diisopropylethylamine (0.30 ml) was added thereto. The reaction solution was diluted with N,N-dimethylformamide (24.0 ml), and dropwise added to an N,N-dimethylformamide solution (5.0 ml) of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (28 mg, 0.070 mmol). This reaction solution was stirred at room temperature for 18 hours. Water (5 ml) was added to stop the reaction. The solvent was distilled off under reduced pressure. A saturated aqueous sodium bicarbonate solution (20 ml) was added to the residue, and extracted three times with ethyl acetate (20 ml). The organic layers were combined together and washed with a saturated aqueous sodium chloride solution (20 ml). The washed organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified by thin layer silica gel chromatography (developing solvent: ethyl acetate:methanol=15:1) to yield 4-amino-18,20-dimethyl-13-oxetan-3-yl-7-thia-3,5,11,15-tetraazatricyclo[15.3.1.12,6]docosa-1(20),2(22),3,5,17(21),18-hexaene-10,16-dione (Compound 72)(3 mg) as a white solid material.

Workup

  1. additionwas added
  2. customthe reaction
  3. distillationThe solvent was distilled off under reduced pressure
  4. additionA saturated aqueous sodium bicarbonate solution (20 ml) was added to the residue
  5. extractionextracted three times with ethyl acetate (20 ml)
  6. washwashed with a saturated aqueous sodium chloride solution (20 ml)
  7. dry with materialThe washed organic layer was dried over anhydrous sodium sulfate
  8. filtrationAfter filtration
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe resulting crude product was purified by thin layer silica gel chromatography (developing solvent: ethyl acetate:methanol=15:1)

Sources & evidence

ORD record
ord-76e948f7881d4646b7528bd007c34a02
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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