Sodium Iodide → HCID 67324316, compound

HRID 1616892Notes

Reaction equation

HRID 1616892 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]2[C:14]3[CH:20]=[CH:19][C:18]([S:21]([C:24]4[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([O:31][CH2:32]CCCl)[CH:25]=4)(=[O:23])=[O:22])=[CH:17][C:15]=3[O:16][CH:10]2[CH2:9]1)=O)(C)(C)C.[I-].[Na+].C(=O)([O-])[O-].[K+].[K+].[CH:44]([N:47]([CH2:51][CH3:52])[CH:48]([CH3:50])[CH3:49])([CH3:46])C.C(#N)C>>[F:30][C:28]1[CH:29]=[C:24]([S:21]([C:18]2[CH:19]=[CH:20][C:14]3[CH:11]4[CH2:12][CH2:13][NH:8][CH2:9][CH:10]4[O:16][C:15]=3[CH:17]=2)(=[O:23])=[O:22])[CH:25]=[C:26]([O:31][CH2:32][CH2:52][CH2:51][N:47]2[CH2:44][CH2:46][CH2:50][C@H:48]2[CH3:49])[CH:27]=1

Participants

6

Reactant 5

HCID 5238Sodium IodideHCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 68305705HCID 68305705, compound

Product 1

HCID 67324316HCID 67324316, compound

Conditions

Temperature
70 °C

Procedure

A mixture of 7-[3-(3-chloro-propoxy)-5-fluoro-benzenesulfonyl]-3,4,4a,9a-tetrahydro-1H-benzofuro[2,3-c]pyridine-2-carboxylic acid tert-butyl ester (100 mg, 0.2 mmol), (R)-2-methyl-pyrrolidine, benzenesulfonic acid salt (92.5 mg, 0.380 mmol), sodium iodide (28.5 mg, 0.190 mmol), potassium carbonate (78.8 mg, 0.570 mmol), N,N-diisopropylethylamine (99.3 uL, 0.570 mmol) in acetonitrile (8.04 mL, 154 mmol) was heated at 70° C. After 3 days the reaction was cooled to room temperature, diluted with 10 mL solvent (MeOH:CH2Cl2 1:1) and filtered through a pad of silica-gel. The filtrate was concentrated. Purification by preparative TLC (MeOH:CH2Cl2 1:9) followed by removal of N-Boc protecting group with 4N HCl using the general procedure described afforded the desired product. mp 208-212° C., MS m/z 475 [M+H]+. 1H-NMR (400 MHz, DMSOd6): δ 10.58 (br s, 1H), 9.52 (br s, 1H), 8.84 (br s, 1H), 7.58 (m, 2H), 7.49 (s, 1H), 7.43 (d, J=6.82 Hz, 1H), 7.34 (s, 1H), 7.22 (d, J=9.92 Hz, 1H), 4.95 (s, 1H), 4.19 (s, 2H), 4.03 (m, 1H), 3.58-3.31 (overlapping m & s, 4H), 3.04 (s, 2H), 2.94 (s, 2H), 2.16 (br s, 4H), 1.99 (s, 1H), 1.94 (br s, 2H), 1.40 (d, J=5.33 Hz, 3H), 1.17 (m, 2H).

Workup

  1. temperatureAfter 3 days the reaction was cooled to room temperature
  2. filtrationfiltered through a pad of silica-gel
  3. concentrationThe filtrate was concentrated
  4. customPurification by preparative TLC (MeOH:CH2Cl2 1:9)
  5. customfollowed by removal of N-Boc protecting group with 4N HCl using the general procedure

Sources & evidence

ORD record
ord-67e345272faf464cb5f298d6ec30918f
Source dataset
uspto-grants-2014_07
Patent number
US08765779B2

Reaction notes

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