Dimethylformamide → HCID 71007644, compound

HRID 1469576Notes

Reaction equation

HRID 1469576 reaction equation
[CH3:1][C:2]1[CH:14]=[N:13][C:12]2[N:11]([CH2:15][CH2:16][C:17]3[CH:18]=[CH:19][C:20]([C:23](O)=[O:24])=[N:21][CH:22]=3)[C:10]3[CH2:9][CH2:8][N:7]4[CH2:26][CH2:27][CH2:28][CH:6]4[C:5]=3[C:4]=2[CH:3]=1.C(Cl)(=O)C(Cl)=O.C[N:36](C=O)C>C(Cl)Cl>[CH3:1][C:2]1[CH:14]=[N:13][C:12]2[N:11]([CH2:15][CH2:16][C:17]3[CH:18]=[CH:19][C:20]([C:23]([NH2:36])=[O:24])=[N:21][CH:22]=3)[C:10]3[CH2:9][CH2:8][N:7]4[CH2:26][CH2:27][CH2:28][CH:6]4[C:5]=3[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 68284113HCID 68284113, compound

Product 1

HCID 71007644HCID 71007644, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

5-[2-(9-Methyl-1,2,3,4,5,10c-hexahydro-3a,6,7-triaza-cyclopenta[c]fluoren-6-yl)-ethyl]-pyridine-2-carboxylic acid (400 mg, 1.063 mmol) was dissolved in 15 mL DCM and cooled at 0° C. Oxalyl chloride (669 mg, 5.315 mmol) and catalytic amount of DMF was added and the reaction mixture was stirred at RT for 1 h. The reaction was monitored by LCMS. The reaction mixture was concentrated and aqueous ammonia was added at 0° C. The reaction mixture was warmed to RT and stirred for 1 h. The reaction mixture was concentrated to obtain the crude product that was purified by reverse phase chromatography to obtain 2.5 mg of 5-[2-(9-methyl-1,2,3,4,5,10c-hexahydro-3a,6,7-triaza-cyclopenta[c]fluoren-6-yl)-ethyl]-pyridine-2-carboxylic acid amide as the TFA salt. 1H NMR TFA: —CD3OD: 8.2 (s, 2H), 7.95 (d, 1H), 7.8 (s, 1H), 7.6 (d, 1H), 5.0 (t, 1H), 4.6 (m, 2H), 3.62 (m, 1H), 3.5 (m, 2H), 3.3 (m, 3H), 2.8 (d, 1H), 2.63 (m, 2H), 2.4 (s, 3H), 2.2 (m, 2H), 2.1 (m, 1H). Separation by chiral HPLC provides enantiomers II-243a-b.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionaqueous ammonia was added at 0° C
  3. temperatureThe reaction mixture was warmed to RT
  4. stirringstirred for 1 h
  5. concentrationThe reaction mixture was concentrated
  6. customto obtain the crude product that
  7. customwas purified by reverse phase chromatography

Sources & evidence

ORD record
ord-9adb909de95b4e8fa7ed2d34ec9ec66a
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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