1,2-Dichloroethane → HCID 86663004, compound

HRID 1811182Notes

Reaction equation

HRID 1811182 reaction equation
[C:1]([C:4]1[C:16]2[NH:15][C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:17]([OH:20])([CH3:19])[CH3:18])[CH:13]=3)[C:8]=2[C:7](C2C(C)=C(N3C(=O)CC(C(O)=O)C3)C=CC=2)=[CH:6][CH:5]=1)(=[O:3])[NH2:2].CNC.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>C1COCC1.C(Cl)Cl.CN(C=O)C>[OH:20][C:17]([C:12]1[CH:13]=[C:14]2[C:9]([C:8]3[CH:7]=[CH:6][CH:5]=[C:4]([C:1]([NH2:2])=[O:3])[C:16]=3[NH:15]2)=[CH:10][CH:11]=1)([CH3:18])[CH3:19]

Participants

8

Reactant 4

HCID 111,2-Dichloroethane2×HCID 674Dimethylamine2×HCID 757711-Hydroxybenzotriazole2×HCID 66606451HCID 66606451, compound2×

Product 1

HCID 86663004HCID 86663004, compoundYield 29.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-(3-(1-carbamoyl-7-(2-hydroxypropan-2-yl)-9H-carbazol-4-yl)-2-methylphenyl)-5-oxopyrrolidine-3-carboxylic acid (Intermediate 81-27, 49 mg, 0.101 mmol), dimethylamine (2 M in THF, 0.252 mL, 0.505 mmol), EDC (38.7 mg, 0.202 mmol) and HOBT (30.9 mg, 0.202 mmol) in THF (2 mL) was stirred at rt overnight. Additional dimethylamine (2 M in THF, 0.252 mL, 0.505 mmol), EDC (38.7 mg, 0.202 mmol) and HOBT (30.9 mg, 0.202 mmol) were added along with DMF (0.5 mL) and the mixture was again stirred overnight. The mixture was diluted with DCM, washed with NaHCO3 (aq), dried and concentrated. The residue was purified by preparative HPLC, and the appropriate effluent fractions were made basic with 1 M aqueous sodium hydroxide and extracted twice with DCM. The organic phase was washed with water, dried and concentrated. The residue was purified by column chromatography (eluting with DCM-methanol-ammonia) to provide 4-(3-4-(dimethylcarbamoyl)-2-oxopyrrolidin-1-yl)-2-methylphenyl)-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide as a white solid (8 mg, 15%). 1H NMR (400 MHz, methanol-d4) δ 7.91 (1H, d, J=7.7 Hz), 7.73 (1H, d, J=1.1 Hz), 7.40-7.49 (2H, m), 7.33 (1H, dd, J=6.5, 2.3 Hz), 7.07 (1H, ddd, J=8.5, 1.4, 1.3 Hz), 7.01 (1H, d, J=7.9 Hz), 6.94 (1H, br. s.), 3.84-4.13 (3H, m), 3.13 (3H, 2 s), 2.97 (3H, 2 s), 2.85-2.94 (1H, m), 2.74-2.83 (1H, m), 1.93 (3H, s), 1.57 (6H, 2 s). Mass spectrum m/z 495.1 (M+H—H2O)+.

Workup

  1. washwashed with NaHCO3 (aq)
  2. customdried
  3. concentrationconcentrated
  4. customThe residue was purified by preparative HPLC
  5. extractionextracted twice with DCM
  6. washThe organic phase was washed with water
  7. customdried
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography (eluting with DCM-methanol-ammonia)

Sources & evidence

ORD record
ord-b9de9e9996f4405396358e178581835e
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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