Diisopropylethylamine → HCID 178495713, compound

HRID 1963952Notes

Reaction equation

HRID 1963952 reaction equation
[Cl:1][C:2]1[C:3]([C:23]2[C:28]([Cl:29])=[CH:27][N:26]=[C:25](F)[CH:24]=2)=[N:4][C:5]([N:8]([CH2:16][CH:17]2[CH2:22][CH2:21][CH2:20][O:19][CH2:18]2)C(=O)OC(C)(C)C)=[CH:6][CH:7]=1.[CH3:31][O:32][CH2:33][C@H:34]([NH:36][C@H:37]1[CH2:42][CH2:41][C@H:40]([NH2:43])[CH2:39][CH2:38]1)[CH3:35].CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[Cl:1][C:2]1[C:3]([C:23]2[C:28]([Cl:29])=[CH:27][N:26]=[C:25]([NH:43][C@H:40]3[CH2:39][CH2:38][C@H:37]([NH:36][C@H:34]([CH3:35])[CH2:33][O:32][CH3:31])[CH2:42][CH2:41]3)[CH:24]=2)=[N:4][C:5]([NH:8][CH2:16][C@@H:17]2[CH2:22][CH2:21][CH2:20][O:19][CH2:18]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 66937007racemic tert-butyl 3,5'-dichloro-2'-fluoro-2,4'-bipyridin-6-yl((tetrahydro-2H-pyran-3-yl)methyl)carbamateHCID 178495714HCID 178495714, compound

Product 1

HCID 178495713HCID 178495713, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
110 °C

Procedure

To a scintillation vial was added racemic tert-butyl 3,5′-dichloro-2′-fluoro-2,4′-bipyridin-6-yl((tetrahydro-2H-pyran-3-yl)methyl)carbamate (114 mg, 0.250 mmol), trans-N1-((R)-1-methoxypropan-2-yl)cyclohexane-1,4-diamine (70 mg, 0.376 mmol) and DIPEA (0.088 ml, 0.501 mmol) followed by NMP (0.1 ml). The mixture was heated at 110° C. for 60 hr then concentrated in vacuo. The resulting residue was purified by reverse phase prep HPLC and lyophilized. The resulting white solid was free based by dissolving in EtOAc and then washing with 1M NaOH (×3), water (×2), saturated brine (×2), then dried (Na2SO4), filtered and evaporated under reduced pressure. The resulting residue was then purified by chiral separation chromatography to yield 3,5′-dichloro-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-N6-(((S)-tetrahydro-2H-pyran-3-yl)methyl)-2,4′-bipyridine-2′,6-diamine (mg), LCMS (m/z): 522.1/523.9 (MH+), tR=0.675 min. and 3,5′-dichloro-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-N6-(((R)-tetrahydro-2H-pyran-3-yl)methyl)-2,4′-bipyridine-2′,6-diamine (mg) LCMS 522.1/523.9 (m/z): (MH+), retention time=0.675 min.

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe resulting residue was purified by reverse phase prep HPLC
  3. dissolutionby dissolving in EtOAc
  4. washwashing with 1M NaOH (×3), water (×2), saturated brine (×2)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe resulting residue was then purified by chiral separation chromatography

Sources & evidence

ORD record
ord-fd1b90c49b3443a5880c2e0da5a9875d
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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