2-(Tributylstannyl)pyrimidine → HCID 71294030, compound

HRID 2036038Notes

Reaction equation

HRID 2036038 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C@:13]2([OH:30])[C:20]3[N:16]([CH:17]=[N:18][CH:19]=3)[C@@H:15]([C:21]3[CH:26]=[CH:25][C:24]([C:27]#[N:28])=[CH:23][C:22]=3[F:29])[CH2:14]2)[CH:8]=1)(=O)=O.C([Sn](CCCC)(CCCC)[C:38]1[N:43]=[CH:42][CH:41]=[CH:40][N:39]=1)CCC>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:29][C:22]1[CH:23]=[C:24]([CH:25]=[CH:26][C:21]=1[C@@H:15]1[N:16]2[CH:17]=[N:18][CH:19]=[C:20]2[C@@:13]([OH:30])([C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([C:38]3[N:43]=[CH:42][CH:41]=[CH:40][N:39]=3)[CH:8]=2)[CH2:14]1)[C:27]#[N:28]

Participants

5

Reactant 2

HCID 27632512-(Tributylstannyl)pyrimidineHCID 86678124HCID 86678124, compound

Product 1

HCID 71294030HCID 71294030, compoundYield 11.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 3-((5R,7S)-5-(4-cyano-2-fluorophenyl)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)phenyl trifluoromethanesulfonate (20 mg, 0.043 mmol), 2-tributylstannanyl-pyrimidine (47.4 mg, 0.128 mmol) and palladium tetrakis (9.89 mg, 8.56 μmol) in toluene (400 μL) was allowed to stir at 100° C. for overnight. The crude was cooled and concentrated. The crude was partitioned between water and CH2Cl2. The aq. layer was extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated. The crude was filtered through a plug of silica using EtOAc/heptane. Part of the residue was then purified via HPLC, using 10-90% MeCN/H2O to give 2 mg of the entitled product. MS 398.1 (M+H); LCMS condition B, retention time 0.95 min. 1H NMR (400 MHz, CDCl3) δ ppm 3.06 (dd, 1H), 3.41 (dd, 1H), 5.76-5.90 (m, 1H), 7.04 (s, 1H), 7.14 (t, 1H), 7.28 (t, 1H), 7.34-7.43 (m, 2H), 7.46 (t, 1H), 7.62 (dd, 1H), 7.68 (s, 1H), 8.30-8.40 (m, 1H), 8.52 (t, 1H), 8.73 (d, 2H).

Workup

  1. temperatureThe crude was cooled
  2. concentrationconcentrated
  3. customThe crude was partitioned between water and CH2Cl2
  4. extractionThe aq. layer was extracted with EtOAc
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. filtrationThe crude was filtered through a plug of silica
  10. customPart of the residue was then purified via HPLC

Sources & evidence

ORD record
ord-bd0a94acd6014deda787d73c03cea728
Source dataset
uspto-grants-2013_11
Patent number
US08575160B2

Reaction notes

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