Ethanol → HCID 89579529, compound

HRID 928599Notes

Reaction equation

HRID 928599 reaction equation
[Br:1][C:2]1[C:10]2[C:9]([N:11]3[CH:16]4[CH2:17][CH2:18][CH:12]3[CH2:13][C:14](=O)[CH2:15]4)=[N:8][CH:7]=[N:6][C:5]=2[S:4][CH:3]=1.[CH:20]1([NH2:24])[CH2:23][CH2:22][CH2:21]1.C(O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1(C)C=CC=CC=1>[Br:1][C:2]1[C:10]2[C:9]([N:11]3[CH:16]4[CH2:17][CH2:18][CH:12]3[CH2:13][CH:14]([NH:24][CH:20]3[CH2:23][CH2:22][CH2:21]3)[CH2:15]4)=[N:8][CH:7]=[N:6][C:5]=2[S:4][CH:3]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 75645CyclobutylamineHCID 5049666Sodium triacetoxyborohydrideHCID 89579712HCID 89579712, compound

Product 1

HCID 89579529HCID 89579529, compoundYield 89.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
30 °C

Procedure

8-(5-Bromothieno[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-one (1.5 g, 4.43 mmol) in toluene (60 mL) was treated with cyclobutylamine (3.145 g, 44.3 mmol) and heated with stirring to reflux for 2 h. Ethanol (100 mL) and sodium triacetoxyborohydride (9.347 g, 44.3 mmol) were added and the reaction stirred and warmed at 30° C. over 3 days. The reaction was then concentrated in vacuum to a gum, diluted with ethyl acetate (100 mL) and saturated sodium hydrogen carbonate solution (50 mL) and shaken. The ethyl acetate layer was then separated, dried over sodium sulphate and concentrated in vacuum to give 8-(5-bromothieno[2,3-d]pyrimidin-4-yl)-N-cyclobutyl-8-azabicyclo[3.2.1]octan-3-amine as a yellow solid (1.799 g, 3.97 mmol, 89%). 1H NMR (CDCl3) δ: 1.5 (3H, d, J=12 Hz), 1.65 (3H, br s), 1.93 (2H, br s), 2.1 (2H, d, J=6 Hz), 2.22 (2H, m), 2.4 (2H, m), 3.0 (1H, br s), 3.3 (1H, m), 4.63 (2H, br s), 7.3 (1H, s), 8.45 (1H, s).

Workup

  1. temperatureheated
  2. temperatureto reflux for 2 h
  3. stirringthe reaction stirred
  4. concentrationThe reaction was then concentrated in vacuum to a gum
  5. additiondiluted with ethyl acetate (100 mL) and saturated sodium hydrogen carbonate solution (50 mL)
  6. stirringshaken
  7. customThe ethyl acetate layer was then separated
  8. dry with materialdried over sodium sulphate
  9. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-4442f03a9f624c88b6dbe5e5df719e77
Source dataset
uspto-grants-2016_03
Patent number
US09290511B2

Reaction notes

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