1,2-Dichloroethane → HCID 59374992, compound

HRID 662002Notes

Reaction equation

HRID 662002 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]([C:21]2[C:22]([CH3:36])=[C:23]([N:27]3[C:31](=[O:32])[CH2:30][CH:29]([C:33]([OH:35])=O)[CH2:28]3)[CH:24]=[CH:25][CH:26]=2)=[CH:6][CH:5]=1)(=[O:3])[NH2:2].[CH3:37][NH:38][CH3:39].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>C1COCC1.C(Cl)Cl.CN(C=O)C>[CH3:37][N:38]([CH3:39])[C:33]([CH:29]1[CH2:28][N:27]([C:23]2[C:22]([CH3:36])=[C:21]([C:7]3[C:8]4[C:9]5[C:14](=[CH:13][C:12]([C:17]([OH:20])([CH3:18])[CH3:19])=[CH:11][CH:10]=5)[NH:15][C:16]=4[C:4]([C:1]([NH2:2])=[O:3])=[CH:5][CH:6]=3)[CH:26]=[CH:25][CH:24]=2)[C:31](=[O:32])[CH2:30]1)=[O:35]

Participants

8

Reactant 4

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

Product 1

HCID 59374992HCID 59374992, compoundYield 15.5%

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—H20)+.

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-42c06d74dbc24cd3a4cb9a4c26cb17b3
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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