Dimethylformamide → HCID 178512214, compound

HRID 724522Notes

Reaction equation

HRID 724522 reaction equation
[NH2:1][CH2:2][CH2:3][NH:4][C:5](=[O:32])[C:6]1[CH:31]=[CH:30][C:9]([C:10]([NH:12][C:13]2[CH:17]=[C:16]([C:18](=[O:25])[NH:19][CH2:20][CH2:21][C:22](=[NH:24])[NH2:23])[N:15]([CH2:26][CH:27]3[CH2:29][CH2:28]3)[CH:14]=2)=[O:11])=[CH:8][CH:7]=1.C[N:34]([CH:36]=O)C.C([N:41](C(C)C)CC)(C)C>>[C:22]([CH2:21][CH2:20][NH:19][C:18]([C:16]1[N:15]([CH2:26][CH:27]2[CH2:29][CH2:28]2)[CH:14]=[C:13]([NH:12][C:10](=[O:11])[C:9]2[CH:30]=[CH:31][C:6]([C:5]([NH:4][CH2:3][CH2:2][NH:1][C:36]([NH2:34])=[NH:41])=[O:32])=[CH:7][CH:8]=2)[CH:17]=1)=[O:25])(=[NH:23])[NH2:24]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 58747082HCID 58747082, compound

Product 1

HCID 178512214HCID 178512214, compound

Procedure

To a solution of 150 mg (0.23 mmol) 99 in 5 mL DMF 336.4 mg (2.3 mmol) pyrazole-1-carboxamidine hydrochloride and 396 μL (2.3 mmol) diisopropylethylamine was added. The solution was stirred overnight at ambient temperature. Next morning the solvent was evaporated, the oily residue was dissolved in 20 mL aqueous 0.1% TFA solution and was purified on a preparative reverse phase HPLC column using acetonitrile gradient. The fractions containing the pure product were pooled, evaporated to dryness dissolved in 3 mL methanol and treated with 1 mL 4.0M HCl in dioxane. 100 was precipitated with ether as bis-HCl salt, filtered off and dried to yield 62 mg (49%). MS: 241.70 (M+2H+). 1H-NMR (DMSO d6) 10.22 (s, 1H); 8.72 (s, 2H); 8.61 (t, 1H); 8.38 (s, 2H); 8.02 (t, 1H); 7.72 (s, 4H); 7.52 (t, 1H); 7.11 (d, 3H); 6.70 (d, 2H); 3.85 (d, 2H); 3.26–3.08 (m); 2.34 (m, 2H); 0.90 (m, 2H); 0.19–0.0 (m, 4H);

Workup

  1. customNext morning the solvent was evaporated
  2. dissolutionthe oily residue was dissolved in 20 mL aqueous 0.1% TFA solution
  3. customwas purified on a preparative reverse phase HPLC column
  4. additionThe fractions containing the pure product
  5. customevaporated to dryness
  6. dissolutiondissolved in 3 mL methanol
  7. additiontreated with 1 mL 4.0M HCl in dioxane
  8. custom100 was precipitated with ether as bis-HCl salt
  9. filtrationfiltered off
  10. customdried
  11. customto yield 62 mg (49%)

Sources & evidence

ORD record
ord-5b9afbdcb14b47929f3f54a359940c51
Source dataset
uspto-grants-2006_11
Patent number
US07141680B2

Reaction notes

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