Dimethylformamide → HCID 86623844, compound

HRID 1990924Notes

Reaction equation

HRID 1990924 reaction equation
[C:1]([NH:4][CH2:5][CH2:6][NH:7][C:8]1[C:9]2[CH:22]=[C:21]([C:23]([OH:25])=[O:24])[NH:20][C:10]=2[N:11]=[C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:13]=1)(=[O:3])[CH3:2].CN(C([O:33]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N([CH2:53][CH3:54])CC)C.C[N:56]([CH:58]=[O:59])[CH3:57]>>[O:33]=[C:57]1[CH2:54][CH2:53][C:58](=[O:59])[N:56]1[O:24][C:23]([C:21]1[NH:20][C:10]2[N:11]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:13]=[C:8]([NH:7][CH2:6][CH2:5][NH:4][C:1](=[O:3])[CH3:2])[C:9]=2[CH:22]=1)=[O:25]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 68569057HCID 68569057, compound2×

Product 1

HCID 86623844HCID 86623844, compound

Procedure

General Procedure for the synthesis of amides 26 from acid 30a: TBTU (48 mg, 0.15 mmol) is added to a solution of acid 30a (41 mg, 0.12 mmol) in DMF (1.5 mL), cooled by ice/water. After 30 min, amine 29 or its hydrochloride salt (0.14 mmol) and triethylamine (22 μL, 0.16 mmol if free amine is used, twice the amount if the hydrochloride salt is used) are added, the cooling bath is removed, and the reaction mixture is stirred at ambient temperature until TLC indicates complete consumption of the acid. DMF is then evaporated, the residue is partitioned between EtOAc (15 mL) and water (10 mL), and the aqueous layer is extracted with more EtOAc (3×15 mL). The combined organic layers are washed with 2N NaOH, water (2×) and brine, dried over MgSO4, filtered and concentrated. The crude material is purified by chromatography followed by trituration or crystallization.

Workup

  1. additionare added
  2. customthe cooling bath is removed
  3. customconsumption of the acid
  4. customDMF is then evaporated
  5. customthe residue is partitioned between EtOAc (15 mL) and water (10 mL)
  6. extractionthe aqueous layer is extracted with more EtOAc (3×15 mL)
  7. washThe combined organic layers are washed with 2N NaOH, water (2×) and brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material is purified by chromatography
  12. customfollowed by trituration or crystallization

Sources & evidence

ORD record
ord-ba85fae96e3a47339d76febe98c8d739
Source dataset
uspto-grants-2010_01
Patent number
US07645754B2

Reaction notes

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