Hydrochloric Acid → HCID 67229748, compound

HRID 2067847Notes

Reaction equation

HRID 2067847 reaction equation
Cl.[C@H:2]12[CH2:8][C@H:5]([NH:6][CH2:7]1)[CH2:4][N:3]2[C:9]([C@@:11]1([CH2:25][CH:26]([F:28])[F:27])[CH2:15][CH2:14][C@@H:13]([NH:16][C@@H:17]2[C@H:22]([O:23][CH3:24])[CH2:21][O:20][CH2:19][CH2:18]2)[CH2:12]1)=[O:10].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.C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:78]1[CH:83]=[C:82]([C:84]([F:87])([F:86])[F:85])[N:81]=[CH:80][N:79]=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CS(C)=O>[F:28][CH:26]([F:27])[CH2:25][C@:11]1([C:9]([N:3]2[CH2:4][C@@H:5]3[CH2:8][C@H:2]2[CH2:7][N:6]3[C:78]2[CH:83]=[C:82]([C:84]([F:87])([F:86])[F:85])[N:81]=[CH:80][N:79]=2)=[O:10])[CH2:15][CH2:14][C@@H:13]([NH:16][C@@H:17]2[C@H:22]([O:23][CH3:24])[CH2:21][O:20][CH2:19][CH2:18]2)[CH2:12]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 115428814-Chloro-6-(trifluoromethyl)pyrimidineHCID 67228981HCID 67228981, compound

Product 1

HCID 67229748HCID 67229748, compoundYield 20%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 679Dimethyl SulfoxideSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

The HCl salt of 1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-{[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]carbonyl}-3-(2,2-difluoroethyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol (177 mg, 0.42 mmol) was placed in a flask with 1,4-dioxane (3 ml). To the stirred solution was added Xantphos (36 mg, 0.062 mmol), Pd2(dba)3 (22 mg, 0.024 mmol), Cs2CO3 (350 mg, 1.07 mmol), and 4-chloro-6-(trifluoromethyl)pyrimidine (195 mg, 1.07 mmol) dissolved in 1,4-dioxane (1 ml). DMSO (0.5 ml) was added for solubility and the reaction was heated to 100° C. for 21.5 hours. The reaction was allowed to cool to room temperature and filtered through celite. The filtrate was concentrated under reduced pressure and purified with the Biotage (0-100% methanol/ethyl acetate 15 column volumes) to give 1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-(2,2-difluoroethyl)-3-({(1S,4S)-5-[6-(trifluoromethyl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol as a white foam (43 mg, 20%). LC/MS (M+H)=534.2504 exp, 534.2597 obs; 1H NMR (400 MHz, CDCl3) δ ppm 8.62 (1H), 6.74-6.46 (1H), 5.93-5.62 (1H), 5.29-4.50 (2H), 4.08-4.03 (1H), 3.93-3.88 (1H), 3.77-3.55 (2H), 3.52-3.32 (6H), 3.30-3.21 (3H), 2.76-2.65 (1H), 2.51-2.33 (1H), 2.21-1.84 (7H), 1.70-1.40 (5H)

Workup

  1. temperatureto cool to room temperature
  2. filtrationfiltered through celite
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. custompurified with the Biotage (0-100% methanol/ethyl acetate 15 column volumes)

Sources & evidence

ORD record
ord-6a3f5dfad90447eea1620d5f3421b179
Source dataset
uspto-grants-2012_10
Patent number
US08293903B2

Reaction notes

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