1-Pyrrolidinecarbonyl chloride → HCID 67201308, compound

HRID 1505953Notes

Reaction equation

HRID 1505953 reaction equation
[NH2:1][C:2]1[CH:16]=[N:15][C:5]2[NH:6][C:7]3[CH:12]=[N:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=3[C:4]=2[CH:3]=1.[N:17]1([C:22](Cl)=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18]1.C(=O)(O)[O-].[Na+]>N1C=CC=CC=1.CO.C(Cl)Cl.O>[N:17]1([C:22]([NH:1][C:2]2[CH:16]=[N:15][C:5]3[NH:6][C:7]4[CH:12]=[N:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=4[C:4]=3[CH:3]=2)=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

8

Reactant 3

HCID 709371-Pyrrolidinecarbonyl chlorideHCID 516892Sodium BicarbonateHCID 58266816HCID 58266816, compound

Product 1

HCID 67201308HCID 67201308, compoundYield 11.4%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 3-amino-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (47.9 mg, 0.229 mmol) in pyridine (6.1 mL) was treated with pyrrolidine-1-carbonyl chloride (83.4 μL, 0.755 mmol) and heated at 60° C. for 4 h. The cooled reaction mixture was treated with saturated aqueous sodium bicarbonate solution then diluted with 20% MeOH in DCM and water. The layers were separated, the aqueous phase extracted with 20% MeOH in DCM, and the combined organic phase was dried over sodium sulfate and concentrated in vacuo. The resultant residue was dissolved in DCM/methanol, absorbed onto silica gel, and purified by flash chromatography (silica, 4 g column, Biotage, 1-20% methanol in DCM containing 0 1% 7N ammonia in MeOH). Collecting appropriate fractions afforded a yellow solid which was further purified by preparative HPLC (5-85% MeCN in water (0.1% NH4OH) over 30 min, 35 mL/min) to afford the title compound as an off-white solid (8.0 mg, 11%). 1H NMR (400 MHz, DMSO-D6): 12.92 (s, 1H), 8.78 (s, 1H), 8.70 (dd, J=4.7, 1.4 Hz, 1H), 8.60 (dd, J=7.9, 1.4 Hz, 1H), 7.47 (dd, J=7.9, 4.8 Hz, 1H), 4.71 (dd, J=8.7, 4.6 Hz, 1H), 2.85 (m, 2H), 2.07 (m, 4H), 1.92 (m, 2H). LCMS (Method E): RT=3.36 min, M+H+=307.

Workup

  1. customThe cooled reaction mixture
  2. customThe layers were separated
  3. extractionthe aqueous phase extracted with 20% MeOH in DCM
  4. dry with materialthe combined organic phase was dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. dissolutionThe resultant residue was dissolved in DCM/methanol
  7. customabsorbed onto silica gel
  8. custompurified by flash chromatography (silica, 4 g column, Biotage, 1-20% methanol in DCM containing 0 1% 7N ammonia in MeOH)
  9. customCollecting appropriate fractions
  10. customafforded a yellow solid which
  11. customwas further purified by preparative HPLC (5-85% MeCN in water (0.1% NH4OH) over 30 min, 35 mL/min)

Sources & evidence

ORD record
ord-2f3f3aef4fe44666b63b065144d8a9b3
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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