Dimethyl Sulfoxide → HCID 178505927, compound

HRID 1623312Notes

Reaction equation

HRID 1623312 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[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][CH2:22][C:23]4[CH:28]=[C:27]([F:29])[CH:26]=[C:25]([F:30])[CH:24]=4)[N:16]=3)[C:12]([Cl:31])=[CH:11][N:10]=2)[CH2:4][CH2:3]1.C([O-])([O-])=O.[K+].[K+].CS(C)=O.Br[CH2:43][CH2:44][CH2:45][CH2:46]Br>C(Cl)Cl>[Cl:31][C:12]1[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][CH2:22][C:23]3[CH:24]=[C:25]([F:30])[CH:26]=[C:27]([F:29])[CH:28]=3)[N:16]=2)=[CH:14][C:9]([NH:8][C@H:5]2[CH2:6][CH2:7][C@H:2]([N:1]3[CH2:46][CH2:45][CH2:44][CH2:43]3)[CH2:3][CH2:4]2)=[N:10][CH:11]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 80561,4-DibromobutaneHCID 11430Potassium CarbonateHCID 178511590HCID 178511590, compound

Product 1

HCID 178505927HCID 178505927, compoundYield 55.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a scintillation vial containing N2′-(trans-4-aminocyclohexyl)-5′-chloro-N6-(3,5-difluorobenzyl)-2,4′-bipyridine-2′,6-diamine (12.3 mg, 0.028 mmol) (obtained following example 2) and K2CO3 (15.32 mg, 0.111 mmol) was added DMSO (0.5 ml) and 1,4-dibromobutane (5.98 mg, 0.028 mmol). The reaction mixture was capped and heated at 60° C. for 7 hr. The reaction mixture was diluted with DCM and washed with H2O, sat NaCl. The organic layer was dried over Na2SO4, filtered and concentrated. The crude solid was purified by reverse phase preparative HPLC to yield 5′-chloro-N6-(3,5-difluorobenzyl)-N2′-(trans-4-(pyrrolidin-1-yl)cyclohexyl)-2,4′-bipyridine-2′,6-diamine (7.8 mg, 46.0%), LCMS (m/z): 498.3 (MH+), retention time=0.65 min as a TFA salt after lypholyzing. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.26-1.40 (m, 2H) 1.48-1.62 (m, 2H) 1.85-1.98 (m, 2H)1.99-2.24 (m, 7H) 2.99-3.14 (m, 4H) 3.51-3.68 (m, 3H) 4.54 (s, 2H) 6.69-6.80 (m, 3H) 6.81-6.90 (m, 3H) 7.60-7.69 (m, 1H) 7.94 (s, 1H).

Workup

  1. customThe reaction mixture was capped
  2. washwashed with H2O
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude solid was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-687a50f8e0f945a9b3d7ed774a48b291
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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