Formaldehyde → HCID 89579649, compound

HRID 928600Notes

Reaction equation

HRID 928600 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][CH:14]([NH:19][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.[CH2:24]=O>C(O)=O>[Br:1][C:2]1[C:10]2[C:9]([N:11]3[CH:12]4[CH2:18][CH2:17][CH:16]3[CH2:15][CH:14]([N:19]([CH:20]3[CH2:23][CH2:22][CH2:21]3)[CH3:24])[CH2:13]4)=[N:8][CH:7]=[N:6][C:5]=2[S:4][CH:3]=1

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 89579529HCID 89579529, compound

Product 1

HCID 89579649HCID 89579649, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

8-(5-Bromothieno[2,3-d]pyrimidin-4-yl)-N-cyclobutyl-8-azabicyclo[3.2.1]octan-3-amine (200 mg, 0.5 mmol) in formalin solution (5 mL) and formic acid (5 mL) was heated to 80° C. for 1 h. The reaction was then concentrated in vacuum to a gum, diluted with ethyl acetate (50 mL) and 10% potassium carbonate solution (10 mL) and shaken. The ethyl acetate layer was then separated, dried over sodium sulphate and concentrated in vacuum to give a colourless gum. The gum was chromatographed on a 25 g silica column in a gradient of 2-15% methanol in dichloromethane. The slower running peak was collected to give 8-(5-bromothieno[2,3-d]pyrimidin-4-yl)-N-cyclobutyl-N-methyl-8-azabicyclo[3.2.1]octan-3-amine (165 mg, 0.405 mmol, 81%). 1H NMR (CDCl3) δ: 1.35 (2H, t, J=12 Hz), 1.5-1.7 (4H, m), 1.8-2.0 (6H, m), 2.1 (3H, s), 2.5 (2H, br m), 3.1 (2H, br m), 4.7 (2H, br m), 7.3 (1H, s), 8.4 (1H, s).

Workup

  1. concentrationThe reaction was then concentrated in vacuum to a gum
  2. additiondiluted with ethyl acetate (50 mL) and 10% potassium carbonate solution (10 mL)
  3. customThe ethyl acetate layer was then separated
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated in vacuum
  6. customto give a colourless gum
  7. customThe gum was chromatographed on a 25 g silica column in a gradient of 2-15% methanol in dichloromethane
  8. customwas collected

Sources & evidence

ORD record
ord-9a4a9ec3389f4418bb9c38da8a52abf0
Source dataset
uspto-grants-2016_03
Patent number
US09290511B2

Reaction notes

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