Sodium hydride → tert-butyl N-(4-[[6-(propan-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy]cyclohexyl)carbamate

HRID 525070Notes

Reaction equation

HRID 525070 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:4][CH2:3]1.[H-].[Na+].Cl[C:19]1[C:20]2[CH:27]=[C:26]([CH:28]([CH3:30])[CH3:29])[S:25][C:21]=2[N:22]=[CH:23][N:24]=1>O1CCCC1>[CH3:30][CH:28]([C:26]1[S:25][C:21]2[N:22]=[CH:23][N:24]=[C:19]([O:1][CH:2]3[CH2:7][CH2:6][CH:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[CH2:4][CH2:3]3)[C:20]=2[CH:27]=1)[CH3:29]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1514287cis-4-(tert-Butoxycarbonylamino)cyclohexanolHCID 27576274-Chloro-6-isopropylthieno(2,3-d)pyrimidine

Product 1

HCID 68109905tert-butyl N-(4-[[6-(propan-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy]cyclohexyl)carbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a 100-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of tert-butyl N-(4-hydroxycyclohexyl)carbamate (3.3 g, 15.33 mmol, 1.10 equiv) in tetrahydrofuran (20 mL). This was followed by the addition of sodium hydride (800 mg, 33.33 mmol, 2.36 equiv) in portions at 0-5° C. The resulting solution was stirred for 2.5 h at room temperature. To this was added a solution of commercially available 4-chloro-6-(propan-2-yl)thieno[2,3-d]pyrimidine (3.0 g, 14.10 mmol, 1.00 equiv) in tetrahydrofuran (10 mL) at 5-10° C. The resulting solution was stirred overnight at room temperature. The reaction mixture was cooled to 5-10° C. with a water/ice bath. The reaction was then quenched by the addition of 100 mL of water. The resulting mixture was concentrated under vacuum. The solids were collected by filtration. This resulted in 4.8 g (87%) of tert-butyl N-(4-[[6-(propan-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy]cyclohexyl)carbamate as a yellow solid. MS: m/z 392 (M+H)+.

Workup

  1. customTo a 100-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe resulting solution was stirred overnight at room temperature
  4. temperatureThe reaction mixture was cooled to 5-10° C. with a water/ice bath
  5. customThe reaction was then quenched by the addition of 100 mL of water
  6. concentrationThe resulting mixture was concentrated under vacuum
  7. filtrationThe solids were collected by filtration
  8. customThis resulted in 4.8 g (87%) of tert-butyl N-(4-[[6-(propan-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy]cyclohexyl)carbamate as a yellow solid

Sources & evidence

ORD record
ord-6fc88b6284814b10aadcbd742fb5bdad
Source dataset
uspto-grants-2016_05
Patent number
US09340554B2

Reaction notes

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