Hydrogen Bromide → HCID 58313899, compound

HRID 624757Notes

Reaction equation

HRID 624757 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[CH:28]=[C:27]([CH2:29]O)[S:26][CH:25]=3)[CH:14]=2)C(=O)OC(C)(C)C)[CH2:4][CH2:3]1>ClCCl>[Br:1][CH2:29][C:27]1[S:26][CH: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]=1

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 86714604HCID 86714604, compound

Product 1

HCID 58313899HCID 58313899, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
40 °C

Procedure

Hydrogen bromide (48% in water, 2.5 mL) was added dropwise to tert-butyl cyclopropyl(3-formyl-5-(5-(hydroxymethyl)thiophen-3-yl)pyrazolo[1,5-a]pyrimidine-7-yl)carbamate (561 mg, 1.35 mmol) suspended in dichloromethane (3.5 mL). The solution immediately became dark brown and homogeneous upon addition. The reaction was heated to 40° C. for 3 h, 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 (15-40% EtOAc/hexanes) to provide 5-(5-(bromomethyl)thiophen-3-yl)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde (105 mg, 20%) as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ: 10.26 (s, 1H), 8.44 (s, 1H), 8.12 (d, 1H, J=1.6 Hz), 7.80 (s, 1H), 6.73 (s, 1H), 6.65 (bs, 1H), 4.80 (s, 2H), 2.81 (m, 1H), 1.03-1.09 (m, 2H), 0.84-0.89 (m, 2H). 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 (15-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-5fe11794f02f4490b04c3eba3fda3fa2
Source dataset
uspto-grants-2016_04
Patent number
US09303033B2

Reaction notes

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