Pyridine → HCID 11431525, compound

HRID 2377031Notes

Reaction equation

HRID 2377031 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@@H:16]2[C@@H:20]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[CH2:19][NH:18][CH2:17]2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.N1C=CC=CC=1.[CH3:36][N:37]=[C:38]=[O:39]>C(Cl)Cl>[F:29][C:2]([F:1])([F:28])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@@H:16]2[C@@H:20]([C:21]3[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=3)[CH2:19][N:18]([C:38]([NH:37][CH3:36])=[O:39])[CH2:17]2)[CH3:14])[CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:8]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 12228Methyl IsocyanateHCID 86610908HCID 86610908, compound

Product 1

HCID 11431525HCID 11431525, compoundYield 87.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 25 mg of the product of Step D (0.06 mmol) in 3 mL dry methylene chloride was added 0.01 mL pyridine (0.12 mmol) and 0.007 mL methylisocyanate (0.12 mmol). The resulting reaction mixture was stirred at RT for 1 hr, then the volatiles were removed under vacuum. The residue was purified by prep TLC eluting with methylene chloride/methanol (9/1) to give 25 mg of yellow glass. Further purification was achieved by prep HPLC on Chiralpak AD column eluting with heptanes/ethanol (95/5) to obtain a minor isomer A and the title compound. 1H-NMR (CDCl3) rotamers: δ: 1.43 (d, 3H, 6.5 Hz), 2.86 (2s, 3H), 3.32-3.5 (m, 3H), 3.75-3.90 (m, 3H), 4.20 (br. s, 1H), 4.53 (q, 1H, 6.5 Hz), 6.95 (t, 2H), 7.04 (m, 2H), 7.57 (s, 2H), 7.77 (s, 1H)ppm. MS: 479.1 (MH+) observed.

Workup

  1. customThe resulting reaction mixture
  2. customthe volatiles were removed under vacuum
  3. customThe residue was purified by prep TLC
  4. washeluting with methylene chloride/methanol (9/1)

Sources & evidence

ORD record
ord-27d6a1f8856e48b89e2a241fc2b9b61b
Source dataset
uspto-grants-2008_12
Patent number
US07468437B2

Reaction notes

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