Diisopropylethylamine → N1-(3-Fluoro-4-(2-(1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-phenylmalonamide

HRID 418571

Reaction equation

HRID 418571 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH2:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[N:19]([CH3:23])[CH:20]=[CH:21][N:22]=3)[S:17][C:10]=12.[O:25]=[C:26]([NH:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:27][C:28](O)=[O:29].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([NH:24][C:28](=[O:29])[CH2:27][C:26]([NH:31][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)=[O:25])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[N:19]([CH3:23])[CH:20]=[CH:21][N:22]=3)[S:17][C:10]=12

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 2565932-(Phenylcarbamoyl)acetic acidHCID 594244803-Fluoro-4-(2-(1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)benzenamine

Product 1

HCID 56953450N1-(3-Fluoro-4-(2-(1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-phenylmalonamideYield 9.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the amine 9 (80 mg, 0.235 mmol), 3-oxo-3-(phenylamino)propanoic acid (1) (42 mg, 0.235 mmol) and BOP (114.6 mg, 0.259 mmol) in DMF (2.4 mL), DIPEA (0.164 mL, 0.941 mmol) was added and the mixture was stirred at room temperature for 2 h. The reaction mixture was partitioned between EtOAc and water. Organic phase was collected, washed with H2O and brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by flash chromatography (EtOAc/MeOH 95:5) followed by crystallization (MeOH) to afford the title compound 5b (11 mg, 9% yield). 1H NMR (DMSO-d6) δ (ppm): 10.55 (s, 1H), 10.19 (s, 1H), 8.5 (d, J=5.4 Hz, 1H), 7.86 (m, 2H), 7.59 (m, 2H), 7.49 (t, J=8.8 Hz, 1H), 7.41 (m, 2H), 7.30 (m, 2H), 7.05 (m, 2H), 6.69 (d, J=5.4 Hz, 1H), 3.99 (s, 3H), 3.52 (s, 2H). MS (m/z): 502.2 (M+H).

Workup

  1. customThe reaction mixture was partitioned between EtOAc and water
  2. customOrganic phase was collected
  3. washwashed with H2O and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (EtOAc/MeOH 95:5)
  7. customfollowed by crystallization (MeOH)

Sources & evidence

ORD record
ord-6a21e4619f75440cb4941ef5ebbd53f8
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Linked notes

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