1,1'-Carbonyldiimidazole → HCID 178458687, compound

HRID 518636Notes

Reaction equation

HRID 518636 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:39]=[CH:40][CH:41]=1)[C:5](/[N:7]=[C:8]1/[N:9]([C@@H:30]2[CH2:35][CH2:34][C@H:33]([C:36](O)=[O:37])[CH2:32][CH2:31]2)[C:10]2[CH:15]=[C:14]([O:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][CH:22]([C:25]([OH:28])([CH3:27])[CH3:26])[CH2:21][CH2:20]3)[N:13]=[CH:12][C:11]=2[NH:29]/1)=[O:6].C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[F:55][C:56]1([F:60])[CH2:59][NH:58][CH2:57]1>CN(C=O)C.C(Cl)Cl>[F:55][C:56]1([F:60])[CH2:59][N:58]([C:36]([C@@H:33]2[CH2:34][CH2:35][C@H:30]([N:9]3[C:10]4[CH:15]=[C:14]([O:16][CH2:17][CH2:18][N:19]5[CH2:20][CH2:21][CH:22]([C:25]([OH:28])([CH3:26])[CH3:27])[CH2:23][CH2:24]5)[N:13]=[CH:12][C:11]=4[NH:29]/[C:8]/3=[N:7]\[C:5](=[O:6])[C:4]3[CH:39]=[CH:40][CH:41]=[C:2]([F:1])[CH:3]=3)[CH2:31][CH2:32]2)=[O:37])[CH2:57]1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 178458688HCID 178458688, compound

Product 1

HCID 178458687HCID 178458687, compoundYield 61.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of cis-4-((E)-2-(3-fluorobenzoylimino)-6-(2-(4-(2-hydroxypropan-2-yl)piperidin-1-yl)ethoxy)-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)cyclohexanecarboxylic acid (0.05 g, 0.088 mmol) in DMF (1 mL) was added CDI (0.029 g, 0.176 mmol), and the resulting mixture was stirred at RT for 1 hour. To this mixture was added 3,3-difluoroazetidine hydrochloride (0.057 g, 0.440 mmol), and the mixture was stirred at RT for 1 hour. The mixture was diluted with DCM (10 mL) and washed with aqueous NH4Cl (5 mL) and brine (5 mL). The organic layer was collected, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by HPLC (5-75% ACN/H2O; 0.1% TFA) to afford (E)-N-(1-(cis-4-(3,3-difluoroazetidine-1-carbonyl)cyclohexyl)-6-(2-(4-(2-hydroxypropan-2-yl)piperidin-1-yl)ethoxy)-1H-imidazo[4,5-c]pyridin-2(3H)-ylidene)-3-fluorobenzamide (35 mg, 61.8% yield). MS m/z=643.2 [M+H]. Calc'd for C33H41F3N6O4: 642.3.

Workup

  1. stirringthe mixture was stirred at RT for 1 hour
  2. washwashed with aqueous NH4Cl (5 mL) and brine (5 mL)
  3. customThe organic layer was collected
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by HPLC (5-75% ACN/H2O; 0.1% TFA)

Sources & evidence

ORD record
ord-3b960e1ccab84314a808ea40fa5911ed
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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