5,7-Dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde → 2-(4-{2-[2-Cyclopentyl-5-(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-ylmethyl)-4,6-dioxo-tetrahydro-pyran-2-yl]-ethyl}-2-fluoro-phenyl)-2-ethyl-butyronitrile

HRID 858629Notes

Reaction equation

HRID 858629 reaction equation
[CH:1]1([C:6]2([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([CH2:27][CH3:28])([CH2:25][CH3:26])[C:23]#[N:24])=[C:18]([F:29])[CH:17]=3)[CH2:11][C:10](=[O:12])[CH2:9][C:8](=[O:13])[O:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:30][C:31]1[CH:36]=[C:35]([CH3:37])[N:34]2[N:38]=[C:39]([CH:41]=O)[N:40]=[C:33]2[N:32]=1>CO>[CH:1]1([C:6]2([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([CH2:27][CH3:28])([CH2:25][CH3:26])[C:23]#[N:24])=[C:18]([F:29])[CH:17]=3)[CH2:11][C:10](=[O:12])[CH:9]([CH2:41][C:39]3[N:40]=[C:33]4[N:32]=[C:31]([CH3:30])[CH:36]=[C:35]([CH3:37])[N:34]4[N:38]=3)[C:8](=[O:13])[O:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 236352265,7-Dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehydeHCID 252323432-{4-[2-(2-Cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl)-2-ethyl-butyronitrile

Product 1

HCID 688664602-(4-{2-[2-Cyclopentyl-5-(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-ylmethyl)-4,6-dioxo-tetrahydro-pyran-2-yl]-ethyl}-2-fluoro-phenyl)-2-ethyl-butyronitrile

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2-{4-[2-(2-cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-2-ethyl-butyronitrile (300 mg, 0.75 mmol) in anhydrous MeOH (3.0 mL) was treated with 5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde (198 mg, 1.1 mmol), followed by borane-dimethylamine complex (62 mg, 1.05 mmol) at room temperature. The reaction was stirred for 12 hours before it was quenched by the addition of CH2Cl2 (30 mL) and Amberlite IR 120(plus) (3 g). The reaction was stirred for 30 minutes, and then filtered. The filtrate was concentrated to an oil, dissolved in CH2Cl2 (25 mL, and then washed with 10 mL 1 N HCl. The aqueous layer was extracted with 2×25 mL CH2Cl2. The organic layers were combined and dried over Na2SO4. After removing the solids by filtration, the liquid was concentrated to an oil. The desired product was isolated by preparatory HPLC (76 mg, 18%). 1H NMR (400 MHz, CDCl3) δ: 0.74 (t, J=7.45 Hz, 6 H), 1.37–1.59 (m, 8 H), 1.79–1.88 (m, 4 H), 1.94–2.03 (m, 2 H), 2.21 (t, J=8.84 Hz, 3 H), 2.36 (d, J=17.94 Hz, 1 H), 2.47–2.55 (m, 5 H), 2.59–2.63 (m, 4 H), 3.95 (d, J=3.54 Hz, 2 H), 6.66 (dd, J1=13.26 Hz, J2=1.64 Hz, 1 H), 6.72–6.75 (m, 2 H), 7.23 (t, J=8.21 Hz, 1 H).

Workup

  1. customfollowed by borane-dimethylamine complex (62 mg, 1.05 mmol) at room temperature
  2. customwas quenched by the addition of CH2Cl2 (30 mL) and Amberlite IR 120(plus) (3 g)
  3. stirringThe reaction was stirred for 30 minutes
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated to an oil
  6. dissolutiondissolved in CH2Cl2 (25 mL
  7. washwashed with 10 mL 1 N HCl
  8. extractionThe aqueous layer was extracted with 2×25 mL CH2Cl2
  9. dry with materialdried over Na2SO4
  10. customAfter removing the solids
  11. filtrationby filtration
  12. concentrationthe liquid was concentrated to an oil

Sources & evidence

ORD record
ord-95f94ae7d4a54c90a551136d79eedb23
Source dataset
uspto-grants-2006_12
Patent number
US07148226B2

Reaction notes

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