Dimethylformamide → HCID 131723038, compound

HRID 393081Notes

Reaction equation

HRID 393081 reaction equation
C(N(C(C)C)CC)(C)C.Cl.COC(=O)[C@H](C[C:17]([C:19]1[S:20][CH:21]=[CH:22][CH:23]=1)=[O:18])N.[Cl:25][C:26]1[CH:34]=[C:33]([C:35]([NH:37][CH2:38][C:39]2[CH:44]=[C:43]([OH:45])[CH:42]=[C:41]([OH:46])[CH:40]=2)=[O:36])[CH:32]=[CH:31][C:27]=1[C:28]([OH:30])=O.CN(C(O[N:55]1N=[N:62][C:57]2[CH:58]=CC=C[C:56]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N([OH:80])N=NC=2C=1.CN(C)[CH:83]=[O:84]>>[Cl:25][C:26]1[CH:34]=[C:33]([C:35]([NH:37][CH2:38][C:39]2[CH:44]=[C:43]([OH:45])[CH:42]=[C:41]([OH:46])[CH:40]=2)=[O:36])[CH:32]=[CH:31][C:27]=1[C:28]([NH:62][C@H:57]([C:58]([O:84][CH3:83])=[O:80])[CH2:56][NH:55][C:17]([C:19]1[S:20][CH:21]=[CH:22][CH:23]=1)=[O:18])=[O:30]

Participants

7

Reactant 6

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 226612932-Chloro-4-[[[(3,5-dihydroxy)phenyl]methyl]amino]carbonylbenzoic acidHCID 68820410HCID 68820410, compound

Product 1

HCID 131723038HCID 131723038, compoundYield 41%

Procedure

Diisopropylethylamine (0.40 g, 3.09 mmol) was added to an ice-bath cooled solution of 3-(thiophene-2-carbonyl)-L-alanine methyl ester hydrochloride (Example XX; 0.33 g, 1.25 mmol), 2-chloro-4-[[[(3,5-dihydroxy)phenyl]methyl]amino]carbonylbenzoic acid (0.40 g,1.24 mmol), HBTU (500 mg, 1.3 mmol), and HOBT (180 mg, 1.3 mmol) in N,N-dimethylformamide (10 mL). The solution was allowed to stir at room temperature overnight. It was then concentrated to remove most of the N,N-dimethylformamide. Ethyl acetate (200 mL) was added, followed by water (200 mL) and 1 M HCl (100 mL). The layers were separated; the ethyl acetate layer was washed with brine (200 mL), dried (MgSO4), and evaporated to give N-[2-chloro-4-[[[(3,5-dihydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[thiophene-2-carbonyl]amino-L-alanine, methyl ester as a white solid (270 mg, 41%), mp 120-123° C.

Workup

  1. concentrationIt was then concentrated
  2. customto remove most of the N,N-dimethylformamide
  3. additionEthyl acetate (200 mL) was added
  4. customThe layers were separated
  5. washthe ethyl acetate layer was washed with brine (200 mL)
  6. dry with materialdried (MgSO4)
  7. customevaporated

Sources & evidence

ORD record
ord-b084fade966b4f1c97bd77d33e280879
Source dataset
uspto-grants-2004_10
Patent number
US06803384B2

Reaction notes

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