Methanol → HCID 178452364, compound

HRID 518663Notes

Reaction equation

HRID 518663 reaction equation
[NH2:1][C:2]1[C:3]([NH:17][C@@H:18]2[CH2:23][CH2:22][C@H:21]([C:24]([N:26]3[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]3)=[O:25])[CH2:20][CH2:19]2)=[CH:4][C:5]([O:8][CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[N:6][CH:7]=1.[C:39]([C:41]1[CH:51]=[CH:50][C:44]([C:45]([N:47]=[C:48]=S)=[O:46])=[CH:43][CH:42]=1)#[N:40].C1N=CN(C(N2C=NC=C2)=O)C=1.CO>C1COCC1>[NH4+:1].[OH-:8].[C:39]([C:41]1[CH:51]=[CH:50][C:44]([C:45](/[N:47]=[C:48]2/[N:17]([C@@H:18]3[CH2:19][CH2:20][C@H:21]([C:24]([N:26]4[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]4)=[O:25])[CH2:22][CH2:23]3)[C:3]3[CH:4]=[C:5]([O:8][CH2:9][CH2:10][N:11]4[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]4)[N:6]=[CH:7][C:2]=3[NH:1]/2)=[O:46])=[CH:43][CH:42]=1)#[N:40]

Participants

7

Reactant 4

HCID 887MethanolHCID 682631,1'-CarbonyldiimidazoleHCID 22908117HCID 22908117, compoundHCID 178452366HCID 178452366, compound

Product 2

HCID 14923Ammonium HydroxideHCID 178452364HCID 178452364, compoundYield 175.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

tert-Butyl 4-(cis-4-(5-amino-2-(2-(piperidin-1-yl)ethoxy)pyridin-4-ylamino)cyclohexanecarbonyl)piperazine-1-carboxylate (0.200 g, 0.377 mmol) was suspended in THF (3.77 mL), and the mixture was cooled to 0° C. under a nitrogen atmosphere. To this mixture was added a solution of 4-cyanobenzoyl isothiocyanate (0.078 g, 0.415 mmol) in 1.5 mL of THF. The reaction was stirred at RT for 30 minutes. PS-CDI (1.417 g, 1.884 mmol) was added (along with 6 mL of THF to account for swelling of the polymer-supported reagent) and the reaction was heated at 60° C. for 1 hour. The solids were filtered off (rinsing well with THF) and the filtrate was concentrated in vacuo. The residual material was purified via silica gel chromatography eluting with a gradient of 0% to 100% 90:10:1 DCM:MeOH:NH4OH, to provide tert-butyl 4-(cis-4-((E)-2-(4-cyanobenzoylimino)-6-(2-(piperidin-1-yl)ethoxy)-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)cyclohexane-carbonyl)piperazine-1-carboxylate as an orange solid (0.227 g, 88% yield). MS m/z=685.2 [M+H], calc 684.83 for C37H48N8O5.

Workup

  1. temperaturewas heated at 60° C. for 1 hour
  2. filtrationThe solids were filtered off (
  3. washrinsing well with THF) and the filtrate
  4. concentrationwas concentrated in vacuo
  5. customThe residual material was purified via silica gel chromatography
  6. washeluting with a gradient of 0% to 100% 90:10:1 DCM

Sources & evidence

ORD record
ord-17df7f5767d440ea8f67983493b14949
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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