Cesium carbonate → HCID 67230028, compound

HRID 1844323Notes

Reaction equation

HRID 1844323 reaction equation
Cl.Cl.[C@H:3]12[CH2:9][C@H:6]([NH:7][CH2:8]1)[CH2:5][N:4]2[C:10]([C@@:12]1([C:26]2([OH:30])[CH2:29][CH2:28][CH2:27]2)[CH2:16][CH2:15][C@@H:14]([NH:17][C@@H:18]2[C@H:23]([O:24][CH3:25])[CH2:22][O:21][CH2:20][CH2:19]2)[CH2:13]1)=[O:11].I[C:32]1[CH:37]=[N:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[N:33]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.CS(C)=O.[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[NH3:4].[OH:30][C:26]1([C@:12]2([C:10]([N:4]3[CH2:5][C@@H:6]4[CH2:9][C@H:3]3[CH2:8][N:7]4[C:32]3[CH:37]=[N:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[N:33]=3)=[O:11])[CH2:16][CH2:15][C@@H:14]([NH:17][C@@H:18]3[C@H:23]([O:24][CH3:25])[CH2:22][O:21][CH2:20][CH2:19]3)[CH2:13]2)[CH2:29][CH2:28][CH2:27]1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 200966762-Iodo-6-(trifluoromethyl)pyrazineHCID 67228799HCID 67228799, compound

Product 2

HCID 222AmmoniaYield 2%HCID 67230028HCID 67230028, compoundYield 82%

Reagents, catalysts & solvents 3

HCID 44556509Tris(dibenzylideneacetone) palladiumCatalystHCID 679Dimethyl SulfoxideSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 93 mg (0.20 mmol) of 1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-ylcarbonyl]-3-(1-hydroxycyclobutyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol dihydrochloride 121 mg (0.442 mmol) of 2-iodo-6-trifluoromethylpyrazine, 326 mg (1.0 mmol) of cesium carbonate, 24 mg (40 umol) of XantPhos, and 16 mg (28 umol) of tris(dibenzylideneacetone) palladium (0) in 0.8 mL of dioxane and 0.4 mL of DMSO was heated at 80 C under argon for 18 h, then cooled and partitioned between ethyl acetate and water. The organic phase was dried (Na2SO4) and concentrated under reduced pressure. Flash chromatography of the residue on silica using 0-2-4% methanolic ammonia and 3% methanol in dichloromethane afforded 89 mg (82%) of the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.51-2.40 (m, 16H) 2.65-2.74 (m, 1H) 3.09-3.49 (m, 10H) 3.54 (d, J=9.6 Hz, 1H) 3.61-3.80 (m, 2H) 3.88-3.96 (m, 1H) 4.06 (dd, J=12.5, 2.9 Hz, 1H) 4.96 (br. s., 1H) 5.21 (br. s., 1H) 8.02 (s, 1H) 8.15 (s, 1H). HRMS calculated for C26H36N5O4F3: 540.2797. found: 540.2896.

Workup

  1. temperaturecooled
  2. custompartitioned between ethyl acetate and water
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fb1be6b9523f4245909755fcb87917f3
Source dataset
uspto-grants-2015_02
Patent number
US08946413B2

Reaction notes

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