Hydrogen Bromide → HCID 58314905, compound

HRID 2036973Notes

Reaction equation

HRID 2036973 reaction equation
[BrH:1].[CH:2]1([N:5]([C:13]2[N:18]3[N:19]=[CH:20][C:21]([CH:22]=[O:23])=[C:17]3[N:16]=[C:15]([C:24]3[S:25][C:26]([CH2:29]O)=[CH:27][CH:28]=3)[CH:14]=2)C(=O)OC(C)(C)C)[CH2:4][CH2:3]1>ClCCl>[Br:1][CH2:29][C:26]1[S:25][C:24]([C:15]2[CH:14]=[C:13]([NH:5][CH:2]3[CH2:4][CH2:3]3)[N:18]3[N:19]=[CH:20][C:21]([CH:22]=[O:23])=[C:17]3[N:16]=2)=[CH:28][CH:27]=1

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 86714601HCID 86714601, compound

Product 1

HCID 58314905HCID 58314905, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
40 °C

Procedure

Hydrogen bromide (48% in water, 5 mL) was added dropwise to tert-butyl cyclopropyl(3-formyl-5-(5-(hydroxymethyl)thiophen-2-yl)pyrazolo[1,5-a]pyrimidine-7-yl)carbamate (980 mg, 2.4 mmol) suspended in dichloromethane (5 mL). The solution immediately became dark brown and homogeneous upon addition. The reaction was heated to 40° C. for 4 hours, then diluted with dichloromethane (10 mL). The liquid was decanted and the gummy residue was washed with dichloromethane (3×10 mL). The combined liquids were washed successively with sat. NaHCO3 (20 mL) and brine (20 mL), and then dried over MgSO4, filtered and concentrated in vacuo: The residue was triturated with hexanes and then purified via flash column chromatography (10-20% EtOAc/hexanes) to provide 5-(5 -(bromomethyl)thiophen-2-yl)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde (300 mg, 34%) as a yellow solid. LCMS (ES): >95% pure, m/z 378 [M+1]+.

Workup

  1. additionThe solution immediately became dark brown and homogeneous upon addition
  2. customThe liquid was decanted
  3. washthe gummy residue was washed with dichloromethane (3×10 mL)
  4. washThe combined liquids were washed successively with sat. NaHCO3 (20 mL) and brine (20 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was triturated with hexanes
  9. custompurified via flash column chromatography (10-20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-825f97941dfd487cad27a05a7dc619b2
Source dataset
uspto-grants-2013_11
Patent number
US08575177B2

Reaction notes

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