Pyridine → HCID 86701783, compound

HRID 2174136Notes

Reaction equation

HRID 2174136 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[C:12]([C:20]([CH3:27])([CH2:24][CH:25]=[CH2:26])[C:21]([OH:23])=O)[C:13]([O:18][CH3:19])=[CH:14][C:15]=2[CH3:17])[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C=O)C.C(Cl)(=O)C(Cl)=O.[NH2:39][C:40]1[CH:41]=[C:42]([CH:45]=[CH:46][C:47]=1[NH2:48])[C:43]#[N:44].N1C=CC=CC=1>C(Cl)Cl.C1COCC1>[NH2:48][C:47]1[CH:46]=[CH:45][C:42]([C:43]#[N:44])=[CH:41][C:40]=1[NH:39][C:21](=[O:23])[C:20]([C:12]1[C:13]([O:18][CH3:19])=[CH:14][C:15]([CH3:17])=[C:16]2[C:11]=1[CH:10]=[CH:9][N:8]2[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])([CH3:27])[CH2:24][CH:25]=[CH2:26]

Participants

8

Reactant 5

HCID 1049PyridineHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 7372853,4-DiaminobenzonitrileHCID 86701781HCID 86701781, compound

Product 1

HCID 86701783HCID 86701783, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To (±)-2-(1-(tert-butoxycarbonyl)-5-methoxy-7-methyl-1H-indol-4-yl)-2-methylpent-4-enoic acid (Example 156-D) (0.76 g, 2.035 mmol) in DCM (20.35 mL) was added DMF (7.88 μl, 0.102 mmol) and then oxalyl chloride (0.356 ml, 4.07 mmol). After 20 minutes the reaction was concentrated in vacuo. The crude product in THF (5 mL) was added to a mixture of 3,4-diaminobenzonitrile (0.48 g, 3.60 mmol) in THF (5 mL) and pyridine (0.494 ml, 6.11 mmol) at 0° C. After 10 minutes the reaction was stirred at room temperature. After 30 minutes the reaction was heated at 55° C. for 4 hours. At this point the volatiles were removed in vacuo and the crude product was absorbed onto silica to purify via FCC (0-50% EtOAc:heptanes) to obtain the title compound. MS (ESI+) m/z 489.5 (M+H).

Workup

  1. concentrationAfter 20 minutes the reaction was concentrated in vacuo
  2. temperatureAfter 30 minutes the reaction was heated at 55° C. for 4 hours
  3. customAt this point the volatiles were removed in vacuo
  4. customthe crude product was absorbed onto silica
  5. customto purify via FCC (0-50% EtOAc:heptanes)

Sources & evidence

ORD record
ord-66f325013ede42cabf20f6258bc2bddf
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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