Water → HCID 58055089, compound

HRID 1020269Notes

Reaction equation

HRID 1020269 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[C:4]([CH2:7][Cl:8])[N:3]=1.[F:9][C:10]1[CH:11]=[C:12]([CH:17]=[CH:18][CH:19]=1)[CH2:13][N:14]=[C:15]=[O:16].O>CN(C1C=CN=CC=1)C.CN1C(=O)CCC1>[F:9][C:10]1[CH:11]=[C:12]([CH:17]=[CH:18][CH:19]=1)[CH2:13][NH:14][C:15]([NH:1][C:2]1[S:6][N:5]=[C:4]([CH2:7][Cl:8])[N:3]=1)=[O:16]

Participants

6

Reactant 3

HCID 962WaterHCID 6434993-Fluorobenzyl isocyanateHCID 140126043-(Chloromethyl)-1,2,4-thiadiazol-5-amine2×

Product 1

HCID 58055089HCID 58055089, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 5-Amino-3-(chloromethyl)-1,2,4-thiadiazole (Intermediate XXIV) (1 equivalent) and the 3-fluoro-benzyl isocyanate (1.2 equivalents) and DMAP (150 μmol) in NMP (12 ml) was heated in a microwave oven for 30 minutes at 150° C. After cooling to ambient temperature, the brown solution is poured into water (60 ml) and the mixture was extracted with ethyl acetate (5×20 ml). The combined organic layers were partitioned with water (2×20 ml), then brine, and dried over sodium sulphate, filtered and volatiles removed in vacuo. The crude material was first purified by normal phase column chromatography (silica gel, 12-75% ethyl acetate in heptane), followed by reversed phase column chromatography (C18, 10-100% methanol in water) to give a white solid. 1H NMR (300 MHz, d6-DMSO) δ 4.36 (d, 2H), 4.69 (s, 2H), 7.03-7.13 (m, 3H), 7.33-7.38 (m, 1H), 7.45 (t, br, 1H).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (5×20 ml)
  2. customThe combined organic layers were partitioned with water (2×20 ml)
  3. dry with materialbrine, and dried over sodium sulphate
  4. filtrationfiltered
  5. customvolatiles removed in vacuo
  6. customThe crude material was first purified by normal phase column chromatography (silica gel, 12-75% ethyl acetate in heptane)
  7. customto give a white solid

Sources & evidence

ORD record
ord-a4296594f94f4e4d989c459cd4191b18
Source dataset
uspto-grants-2014_05
Patent number
US08716320B2

Reaction notes

Loading…