2-Bromopyridine → HCID 70032920, compound

HRID 431831Notes

Reaction equation

HRID 431831 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:12][C@H:11]([S:13][C:14]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:10][C@H:9]2[CH2:33][O:34][CH2:35][C:36]2[CH:41]=[C:40]([F:42])[C:39]([F:43])=[CH:38][C:37]=2[F:44])=[N:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][N:70]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[N:70]1[CH:71]=[CH:72][CH:73]=[CH:74][C:69]=1[C:2]1[CH:7]=[N:6][C:5]([N:8]2[CH2:12][C@H:11]([S:13][C:14]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:10][C@H:9]2[CH2:33][O:34][CH2:35][C:36]2[CH:41]=[C:40]([F:42])[C:39]([F:43])=[CH:38][C:37]=2[F:44])=[N:4][CH:3]=1

Participants

8

Reactant 5

HCID 79732-BromopyridineHCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 70003684HCID 70003684, compound

Product 1

HCID 70032920HCID 70032920, compoundYield 18.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 0.68 g (1 mmol) (2S,4R)-5-Bromo-2-[2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidin-1-yl]-pyrimidine, 0.28 g (1.1 mmol) bis(pinacolato)diboron, 0.29 g (3 mmol, dried 2 h at 100° C., 0.1 Torr) potassium acetate and 0.024 g (0.03 mmol) PdCl2(dppf) in 12 ml DMF were stirred for 4.5 h at 80° C. The reaction was cooled, treated with 0.195 ml (2 mmol) 2-bromopyridine, 0.024 g (0.03 mmol) PdCl2(dppf) and 2.5 ml aqueous 2 M Na2CO3 solution and heated for 16 h at 80° C. The reaction evaporated (60° C./0.1 torr) and partitioned between water/Et2O (3×). The organic phases were washed with aqueous 10% NaCl and dried over Na2SO4. Purification by flash-chromatography on silica gel (toluene/EtOAc 97.5:2.5) gave 0.125 g (2S,4R)-5-Pyridin-2-yl-2-[2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidin-1-yl]-pyrimidine, MS: 675 (MH+). TFA/triisopropylsilane deprotection (see General method for S-deprotection, Method D) gave (3R,5S)-1-(5-Pyridin-2-yl-pyrimidin-2-yl)-5-(2,4,5-trifluoro-benzyloxymethyl)-pyrrolidine-3-thiol; compound with trifluoro-acetic acid, MS: 433 (MH+).

Workup

  1. temperatureThe reaction was cooled
  2. customThe reaction evaporated (60° C./0.1 torr)
  3. custompartitioned between water/Et2O (3×)
  4. washThe organic phases were washed with aqueous 10% NaCl
  5. dry with materialdried over Na2SO4
  6. customPurification by flash-chromatography on silica gel (toluene/EtOAc 97.5:2.5)

Sources & evidence

ORD record
ord-ab51b923aeae4d97b8ad5a354e75fc44
Source dataset
uspto-grants-2003_12
Patent number
US06660738B2

Reaction notes

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