tert-Butanol → Tert-butyl 3-bromopyrazolo[1,5-a]pyrimidin-2-ylcarbamate

HRID 1912953Notes

Reaction equation

HRID 1912953 reaction equation
[Br:1][C:2]1[C:3](C(O)=O)=[N:4][N:5]2[CH:10]=[CH:9][CH:8]=[N:7][C:6]=12.C([N:16]([CH2:19]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:28])C=CC=CC=1.[C:38]([OH:42])([CH3:41])([CH3:40])[CH3:39]>>[Br:1][C:2]1[C:3]([NH:16][C:19](=[O:28])[O:42][C:38]([CH3:41])([CH3:40])[CH3:39])=[N:4][N:5]2[CH:10]=[CH:9][CH:8]=[N:7][C:6]=12

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 170248123-Bromopyrazolo[1,5-a]pyrimidine-2-carboxylic acid

Product 1

HCID 68749841Tert-butyl 3-bromopyrazolo[1,5-a]pyrimidin-2-ylcarbamate

Procedure

3-Bromopyrazolo[1,5-a]pyrimidine-2-carboxylic acid (1.95 g, 8.06 mmol; Art-Chem) was suspended in tert-butyl alcohol (75 mL). Triethylamine (1.35 mL, 9.67 mmol) and diphenylphosphoryl azide (2.09 mL, 9.67 mmol) was added and the mixture was stirred under refluxing condition for 4 hours. The reaction mixture was cooled to ambient temperature and concentrated under vacuum. The resulting residue was purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 50×100 mm, flow rate 100 mL/minute, 20-75% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound. MS (ESI) m/z 310/313 (M−H)−.

Workup

  1. temperatureunder refluxing condition for 4 hours
  2. concentrationconcentrated under vacuum
  3. customThe resulting residue was purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 50×100 mm, flow rate 100 mL/minute, 20-75% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

Sources & evidence

ORD record
ord-4a9d0390d39d4682bd424d5095f763b4
Source dataset
uspto-grants-2013_12
Patent number
US08609669B2

Reaction notes

Loading…