4-Amino-1-Boc-piperidine → HCID 178521576, compound

HRID 1963867Notes

Reaction equation

HRID 1963867 reaction equation
ClC1C(C2C=CC=C(F)N=2)=CC(N[C@H]2CC[C@H](O)CC2)=NC=1.NC1CCN(C(OC(C)(C)C)=O)CC1.[Cl:37][C:38]1[C:39]([C:52]2[CH:57]=[CH:56][CH:55]=[C:54]([NH:58][CH:59]3[CH2:64][CH2:63][N:62](C(OC(C)(C)C)=O)[CH2:61][CH2:60]3)[N:53]=2)=[CH:40][C:41]([NH:44][C@H:45]2[CH2:50][CH2:49][C@H:48]([OH:51])[CH2:47][CH2:46]2)=[N:42][CH:43]=1>CS(C)=O>[Cl:37][C:38]1[C:39]([C:52]2[CH:57]=[CH:56][CH:55]=[C:54]([NH:58][CH:59]3[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]3)[N:53]=2)=[CH:40][C:41]([NH:44][C@H:45]2[CH2:50][CH2:49][C@H:48]([OH:51])[CH2:47][CH2:46]2)=[N:42][CH:43]=1

Participants

5

Reactant 3

HCID 12682914-Amino-1-Boc-piperidineHCID 178452074HCID 178452074, compoundHCID 178521575HCID 178521575, compound

Product 1

HCID 178521576HCID 178521576, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Conditions

Temperature
105 °C

Procedure

A mixture of trans-4-(5′-chloro-6-fluoro-2,4′-bipyridin-2′-yl-amino)cyclohexanol (15.5 mg, 0.048 mmol), DMSO (0.4 ml), and tert-butyl 4-aminopiperidine-1-carboxylate (48.2 mg, 0.241 mmol) reaction mixture was stirred at 105° C. for 40 hr. LCMS indicated formation of the intermediate tert-butyl 4-(5′-chloro-2′-(trans-4-hydroxycyclohexylamino)-2,4′-bipyridin-6-yl-amino)piperidine-1-carboxylate (LCMS (m/z): 502.4 (MH+), retention time=0.70 min.). The Boc protecting group was removed from the intermediate by adding HCL 6M aq (140 μl, 0.840 mmol) to the crude reaction mixture mixture, followed by stirring the mixture at 90° C. for 45 minutes. The reaction mixture was cooled, 0.5 ml of DMSO was added, filtered and purified by prep LC. Lypholization of the material yielded 9.8 mg of the title compound, as a TFA salt. LCMS (m/z): 402.3 (MH+), retention time=0.41 min.; 1H NMR (300 MHz, METHANOL-d4, 25° C.) δ ppm 1.32-1.52 (m, 4 H) 1.71-1.87 (m, 2 H) 1.96-2.12 (m, 4 H) 2.27 (dd, J=14.21, 3.37 Hz, 2 H) 3.06-3.18 (m, 2 H) 3.39-3.50 (m, 2 H) 3.54-3.68 (m, 2 H) 4.05-4.17 (m, 1 H) 6.72 (d, J=8.50 Hz, 1 H) 6.90 (d, J=7.33 Hz, 1 H) 7.00 (s, 1 H) 7.56-7.64 (m, 1 H) 8.01 (s, 1 H)

Workup

  1. customThe Boc protecting group was removed from the intermediate
  2. additionby adding HCL 6M aq (140 μl, 0.840 mmol) to the crude
  3. customreaction mixture mixture
  4. stirringby stirring the mixture at 90° C. for 45 minutes
  5. temperatureThe reaction mixture was cooled
  6. filtrationfiltered
  7. custompurified by prep LC

Sources & evidence

ORD record
ord-658468f2816c43cc96b72c9287c83dcb
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

Loading…