4-[[6-(Propan-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy]cyclohexan-1-amine hydrochloride → 4-[[6-(Propan-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy]cyclohexan-1-amine

HRID 2369400Notes

Reaction equation

HRID 2369400 reaction equation
Cl.[CH3:2][CH:3]([C:5]1[S:21][C:8]2[N:9]=[CH:10][N:11]=[C:12]([O:13][CH:14]3[CH2:19][CH2:18][CH:17]([NH2:20])[CH2:16][CH2:15]3)[C:7]=2[CH:6]=1)[CH3:4]>C(O)=O>[CH3:4][CH:3]([C:5]1[S:21][C:8]2[N:9]=[CH:10][N:11]=[C:12]([O:13][CH:14]3[CH2:19][CH2:18][CH:17]([NH2:20])[CH2:16][CH2:15]3)[C:7]=2[CH:6]=1)[CH3:2]

Participants

4

Reactant 2

HCID 681098834-[[6-(Propan-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy]cyclohexan-1-amine hydrochlorideHCID 178486302HCID 178486302, compound

Product 1

HCID 681098844-[[6-(Propan-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy]cyclohexan-1-amineYield 12.9%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
110 °C

Procedure

A 100-mL round-bottom flask was charged with 4-[[6-(propan-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy]cyclohexan-1-amine hydrochloride (1.0 g, 3.05 mmol, 1.00 equiv), formic acid (20 mL) and polyoxymethylene (0.9 g). The resulting solution was stirred overnight at 110° C. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 100 mL of water. The pH value of the solution was adjusted to 10 with 3N sodium hydroxide. The resulting solution was extracted with 3×100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3×100 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was purified by preparative HPLC (2#-Waters 2767-2(1-IPLC-08)) under the following conditions: column: Xbridge Prep C18, 5 um, 19*150 mm; mobile phase: water (50 mM NH4HCO3) and CH3CN (10.0% CH3CN up to 35.0% in 2 min, up to 58.0% in 8 min, up to 100.0% in 1 min, down to 10.0% in 1 min); detector: UV 220 nm. This resulted in 114.6 mg (12%) of Compound I-182 as a white solid. 1H NMR: (400 MHz, CDCl3) δ 8.53 (1H, s), 7.01-7.01 (1H, d), 5.19-5.25 (1H, m), 3.19-3.26 (1H, m), 2.40 (7H, s), 2.29-2.32 (2H, d), 2.06-2.08 (2H, d), 1.42-1.63 (4H, m),1.39-1.40 (6H, d). MS: m/z 320 (M+H)+.

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. additionThe resulting solution was diluted with 100 mL of water
  3. extractionThe resulting solution was extracted with 3×100 mL of ethyl acetate
  4. washThe resulting mixture was washed with 3×100 mL of brine
  5. dry with materialThe mixture was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe crude product was purified by preparative HPLC (2#-Waters 2767-2(1-IPLC-08)) under the following conditions
  8. waitmobile phase: water (50 mM NH4HCO3) and CH3CN (10.0% CH3CN up to 35.0% in 2 min
  9. waitup to 58.0% in 8 min
  10. waitup to 100.0% in 1 min
  11. waitdown to 10.0% in 1 min)

Sources & evidence

ORD record
ord-61672694a0424f2fb993e68fd6c5fbf7
Source dataset
uspto-grants-2014_04
Patent number
US08703941B2

Reaction notes

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