Sulfuric Acid → 1-[4-(2-Amino-4-methyl-thiazol-5-yl)-pyridin-2-yl]-cyclobutanecarboxylic acid amide

HRID 1516220Notes

Reaction equation

HRID 1516220 reaction equation
C(OC(=O)[NH:7][C:8]1[S:9][C:10]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([C:20]3([C:24]#[N:25])[CH2:23][CH2:22][CH2:21]3)[CH:15]=2)=[C:11]([CH3:13])[N:12]=1)(C)(C)C.S(=O)(=O)(O)[OH:28]>>[NH2:7][C:8]1[S:9][C:10]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([C:20]3([C:24]([NH2:25])=[O:28])[CH2:23][CH2:22][CH2:21]3)[CH:15]=2)=[C:11]([CH3:13])[N:12]=1

Participants

3

Reactant 2

HCID 1118Sulfuric AcidHCID 59293719{5-[2-(1-Cyano-cyclobutyl)-pyridin-4-yl]-4-methyl-thiazol-2-yl}-carbamic acid tert-butyl ester

Product 1

HCID 592936881-[4-(2-Amino-4-methyl-thiazol-5-yl)-pyridin-2-yl]-cyclobutanecarboxylic acid amide

Conditions

Temperature
0 °C

Procedure

A mixture of {5-[2-(1-cyano-cyclobutyl)-pyridin-4-yl]-4-methyl-thiazol-2-yl}-carbamic acid tert-butyl ester (Step 19.2) (640 mg, 1.73 mmol) and concentrated sulfuric acid is stirred for 40 min at 0° C., allowed to warm to rt, stirred for 1 h, quenched by addition of a saturated solution of NaHCO3 (50 mL) and extracted with DCM (3×75 mL). The organic phase is washed with a saturated solution of NaHCO3 (2×50 mL), dried (Na2SO4), filtered and concentrated. The residue is purified by silica gel column chromatography (DCM/MeOH/NH3aq, 99:0:1→93:6:1) to afford 35 mg of the title compound as a yellow solid: ESI-MS: 289.1 [M+H]+; TLC: Rf=0.32 (DCM/MeOH, 9:1).

Workup

  1. temperatureto warm to rt
  2. stirringstirred for 1 h
  3. customquenched by addition of a saturated solution of NaHCO3 (50 mL)
  4. extractionextracted with DCM (3×75 mL)
  5. washThe organic phase is washed with a saturated solution of NaHCO3 (2×50 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue is purified by silica gel column chromatography (DCM/MeOH/NH3aq, 99:0:1→93:6:1)

Sources & evidence

ORD record
ord-d333d4db62294919828656f7f0df25a4
Source dataset
uspto-grants-2012_07
Patent number
US08227462B2

Reaction notes

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