Bromoacetic Acid → HCID 20653463, compound

HRID 1976810Notes

Reaction equation

HRID 1976810 reaction equation
BrCC(O)=[O:4].C(N=[C:10]=[N:11][CH:12]([CH3:14])C)(C)C.[CH2:15]=[CH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[C:23]([NH:26][C:27]1[S:28][C:29]([S:33](Cl)(=[O:35])=[O:34])=[C:30]([CH3:32])[N:31]=1)(=[O:25])[CH3:24].C[N:38]([CH:40]=[O:41])C>>[CH2:12]([N:11]([CH2:10][C:40]([NH:38][OH:4])=[O:41])[S:33]([C:29]1[S:28][C:27]([NH:26][C:23](=[O:25])[CH3:24])=[N:31][C:30]=1[CH3:32])(=[O:35])=[O:34])[CH2:14][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:17][CH2:16][CH3:15]

Participants

6

Reactant 5

HCID 6227Bromoacetic AcidHCID 6228DimethylformamideHCID 7501StyreneHCID 12734DiisopropylcarbodiimideHCID 969512-Acetamido-4-methylthiazole-5-sulfonyl chloride

Product 1

HCID 20653463HCID 20653463, compoundYield 51%

Procedure

Bromoacetic acid (167 mg, 1.2 mmol) and diisopropylcarbodiimide (94 mm3, 0.6 mmol) were added to a suspension of the resin (4-(O-methylhydroxylamine)phenoxymethyl-copoly(styrene-1% divinylbenzene)-resin (100-200 mesh)) prepared according to Example 1 (250 mg, 0.1 mmol) in DMF (6 cm3). The mixture was agitated for 90 minutes and then the solution was drained from the resin which was washed and dried as described above in Example 1 The resin was soaked in DMSO (2 cm3) and a solution of n-decylamine in DMSO (5 cm3 of a 2M solution, 10 mmol) was added and the mixture shaken for 4 h before the resin was drained and washed thoroughly as before. The resin was then suspended in DMF and 2-acetamido-4-methyl-5-thiazolesulfonylchloride (102 mg, 0.4 mmol) was added. The mixture was heated at 60° for 8 h and then the resin was drained, washed and dried as described previously. Cleavage from the resin as in Example A gave a white solid which was purified by column chromatography (10% methanol-dichloromethane; silica) to give the desired 2-(N-decyl-2-acetamido-4-methylthiazol-5-ylsulfonamido)-acetohydroxamic acid (23 mg, 51%) as a white solid; 1H NMR (CDCl3) δ 3.83 (2H, m), 3.05 (2H, m), 2.52 (3H, s, Me), 2.35 (3H, s, NHCOMe), 1.69 (2H, m), 1.15-1.25 (14H, m, alkyl), 0.87 (3H, t, J=7.2Hz, CH3-alkyl).

Workup

  1. customprepared
  2. washwas washed
  3. customdried
  4. additiona solution of n-decylamine in DMSO (5 cm3 of a 2M solution, 10 mmol) was added
  5. stirringthe mixture shaken for 4 h before the resin
  6. washwashed thoroughly as before
  7. temperatureThe mixture was heated at 60° for 8 h
  8. washwashed
  9. customdried
  10. customCleavage from the resin as in Example A gave a white solid which
  11. customwas purified by column chromatography (10% methanol-dichloromethane; silica)

Sources & evidence

ORD record
ord-0c4037c8df024eb6bbb9925ab05a36dc
Source dataset
uspto-grants-2001_05
Patent number
US06228988B1

Reaction notes

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