Diisopropylethylamine → HCID 178431477, compound

HRID 1963951Notes

Reaction equation

HRID 1963951 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[CH:14]=[C:13]([C:15]3[C:20]([Cl:21])=[CH:19][CH:18]=[C:17]([NH:22][CH2:23][CH:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)[N:16]=3)[C:12]([Cl:30])=[CH:11][N:10]=2)[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.CC1C=CC(S(O[CH2:51][C@@H:52]2[CH2:56][O:55][C:54]([CH3:58])([CH3:57])[O:53]2)(=O)=O)=CC=1>CN(C=O)C.O>[Cl:21][C:20]1[C:15]([C:13]2[C:12]([Cl:30])=[CH:11][N:10]=[C:9]([NH:8][C@H:5]3[CH2:6][CH2:7][C@H:2]([NH:1][CH2:51][C@@H:52]4[CH2:56][O:55][C:54]([CH3:58])([CH3:57])[O:53]4)[CH2:3][CH2:4]3)[CH:14]=2)=[N:16][C:17]([NH:22][CH2:23][CH:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 2723760(S)-(+)-2,2-Dimethyl-1,3-dioxolan-4-ylmethyl p-ToluenesulfonateHCID 178511605HCID 178511605, compound

Product 1

HCID 178431477HCID 178431477, compoundYield 5.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

To a stirred solution of N2′-(trans-4-aminocyclohexyl)-3,5′-dichloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine (68 mg, 0.151 mmol) in DMF (0.2 ml) was added DIPEA (80 μL, 0.458 mmol) followed by (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (42 mg, 0.147 mmol). The mixture was heated at 75° C. for 19 hours. The mixture was allowed to cool, then diluted with water and then extracted with EtOAc (×3). The organics were combined then washed with water (×2), saturated brine (×2), then dried (Na2SO4), filtered and evaporated under reduced pressure. The resulting residue was purified by reverse phase prep HPLC and lyophilized to yield 3,5′-dichloro-N2′-(trans-4-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)aminocyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine (4.4 mg), LCMS (m/z): 564.4/566.3 (bis-chloro isotopic signature for MH+) retention time=0.65 min as a TFA salt.

Workup

  1. temperatureto cool
  2. extractionextracted with EtOAc (×3)
  3. washThe organics were combined then washed with water (×2), saturated brine (×2)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe resulting residue was purified by reverse phase prep HPLC

Sources & evidence

ORD record
ord-652105074600464aa764709a296fd5a2
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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