Triethylamine → 3-(2-Chlorophenyl)-N-[4-chloro-3-[(1H-pyrrolo[2,3-b]pyridin-5-ylamino)carbonyl]phenyl]-5-isoxazolecarboxamide

HRID 564016Notes

Reaction equation

HRID 564016 reaction equation
F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C.[Cl:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[CH:37]1[CH:41]=[C:40]([C:42]([OH:44])=O)[O:39][NH:38]1.[NH2:45][C:46]1[CH:47]=[CH:48][C:49]([Cl:64])=[C:50]([CH:63]=1)[C:51]([NH:53][C:54]1[CH:55]=[C:56]2[CH:62]=[CH:61][NH:60][C:57]2=[N:58][CH:59]=1)=[O:52]>CN(C=O)C>[Cl:64][C:49]1[CH:48]=[CH:47][C:46]([NH:45][C:42]([C:40]2[O:39][N:38]=[C:37]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=3[Cl:30])[CH:41]=2)=[O:44])=[CH:63][C:50]=1[C:51](=[O:52])[NH:53][C:54]1[CH:55]=[C:56]2[CH:62]=[CH:61][NH:60][C:57]2=[N:58][CH:59]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67008119HCID 67008119, compoundHCID 67008363HCID 67008363, compound

Product 1

HCID 670075903-(2-Chlorophenyl)-N-[4-chloro-3-[(1H-pyrrolo[2,3-b]pyridin-5-ylamino)carbonyl]phenyl]-5-isoxazolecarboxamideYield 38.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) (0.084 g, 0.26 mmol) and triethylamine (50 μL, 0.35 mmol) were added to a solution of 3-(2-chloro-phenyl)-2,3-dihydro-isoxazole-5-carboxylic acid (0.058 g, 0.26 mmol) in DMF (1 ml) and the reaction stirred for 10 minutes at room temperature. 5-Amino-2-chloro-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)-benzamide (0.050 g, 0.175 mmol) was added to the reaction mixture and stirred for a further 24 hours. The solvent was removed under reduced pressure then methanol (3 ml) and ammonium hydroxide (1 ml) were added to the residue and the mixture stirred for a further 3 hours. The solvent was removed under reduced pressure and the resultant solid triturated with acetonitrile:water (1:1, 5 ml). The solid was filtered to afford 3-(2-Chloro-phenyl)-isoxazole-5-carboxylic acid [4-chloro-3-(1H-pyrrolo[2,3-b]pyridin-5-ylcarbamoyl)-phenyl]-amide 0.033 g (37% yield)

Workup

  1. stirringstirred for a further 24 hours
  2. customThe solvent was removed under reduced pressure
  3. additionmethanol (3 ml) and ammonium hydroxide (1 ml) were added to the residue
  4. stirringthe mixture stirred for a further 3 hours
  5. customThe solvent was removed under reduced pressure
  6. customthe resultant solid triturated with acetonitrile:water (1:1, 5 ml)
  7. filtrationThe solid was filtered

Sources & evidence

ORD record
ord-2db44b351903442b9c1ef195c0945e2a
Source dataset
uspto-grants-2011_11
Patent number
US08067599B2

Reaction notes

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