1,2-Dichloroethane → 6-{3-[(dimethylamino)methyl]-4-fluorophenyl}-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-indole-4-carboxamide

HRID 873392Notes

Reaction equation

HRID 873392 reaction equation
[CH3:1][N:2]([CH2:4][C:5]1[CH:6]=[C:7]([C:12]2[CH:13]=[C:14]([C:25](O)=[O:26])[C:15]3[C:16]([CH3:24])=[CH:17][N:18]([CH:21]([CH3:23])[CH3:22])[C:19]=3[CH:20]=2)[CH:8]=[CH:9][C:10]=1[F:11])[CH3:3].Cl.[NH2:29][CH2:30][C:31]1[C:32](=[O:39])[NH:33][C:34]([CH3:38])=[CH:35][C:36]=1[CH3:37].C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)CCl>CN(C=O)C>[CH3:1][N:2]([CH2:4][C:5]1[CH:6]=[C:7]([C:12]2[CH:13]=[C:14]([C:25]([NH:29][CH2:30][C:31]3[C:32](=[O:39])[NH:33][C:34]([CH3:38])=[CH:35][C:36]=3[CH3:37])=[O:26])[C:15]3[C:16]([CH3:24])=[CH:17][N:18]([CH:21]([CH3:22])[CH3:23])[C:19]=3[CH:20]=2)[CH:8]=[CH:9][C:10]=1[F:11])[CH3:3]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 438104513-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one hydrochlorideHCID 682099906-{3-[(dimethylamino)methyl]-4-fluorophenyl}-3-methyl-1-(1-methylethyl)-1H-indole-4-carboxylic acid

Product 1

HCID 674673976-{3-[(dimethylamino)methyl]-4-fluorophenyl}-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-indole-4-carboxamideYield 64.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred suspension of 6-{3-[(dimethylamino)methyl]-4-fluorophenyl}-3-methyl-1-(1-methylethyl)-1H-indole-4-carboxylic acid (210 mg, 0.570 mmol), 3-(aminomethyl)-4,6-dimethyl-2(1H)-pyridinone HCl salt (140 mg, 0.742 mmol) and HOAt (100 mg, 0.735 mmol) in DMF (15 mL) was added N-methylmorpholine (82 μl, 0.746 mmol) and EDC free base (110 mg, 0.709 mmol). The reaction was stirred for 4 h at RT and concentrated to near dryness under vacuum. Water was added till the product ppt. out. The suspension was triturated, filtered, rinsed with cold water then dried under vacuum to give the product 6-{3-[(dimethylamino)methyl]-4-fluorophenyl}-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-indole-4-carboxamide (186 mg, 0.370 mmol, 64.9% yield) as a light tan solid. 1H NMR (400 MHz, DMSO-d6) δ=11.47 (br. s., 1 H), 8.15 (t, J=4.9 Hz, 1 H), 8.04 (d, J=5.3 Hz, 1 H), 7.90-7.86 (m, 1 H), 7.39 (t, J=9.2 Hz, 1 H), 7.35 (s, 1 H), 7.27 (d, J=1.3 Hz, 1 H), 5.87 (s, 1 H), 4.88 (dt, J=6.6, 13.3 Hz, 1 H), 4.36 (d, J=5.1 Hz, 2 H), 4.26 (br. s., 2 H), 2.69 (s, 6 H), 2.24 (s, 3 H), 2.17 (s, 3 H), 2.11 (s, 3 H), 1.44 (d, J=6.6 Hz, 6 H). MS(ES)+m/e 503.0 [M+H]+.

Workup

  1. concentrationconcentrated
  2. additionWater was added till the product ppt
  3. customThe suspension was triturated
  4. filtrationfiltered
  5. washrinsed with cold water
  6. customthen dried under vacuum

Sources & evidence

ORD record
ord-74eb4c933b914b9cbf709e7ae53362ad
Source dataset
uspto-grants-2015_03
Patent number
US08975291B2

Reaction notes

Loading…