1,10-Phenanthroline → HCID 118598613, compound

HRID 1050363Notes

Reaction equation

HRID 1050363 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11](NC(C3CC3)=O)[CH:10]=2)[C:5](=[O:21])[N:4]2[C:22]([C:27]3[CH:32]=[CH:31][CH:30]=[C:29](F)C=3)(C)[NH:23][C:24](=[O:25])[C:3]=12.I[C:35]1[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=1.C(=O)([O-])[O-].[Cs+].[Cs+].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>CN(C)C=O.[Cu]I>[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:10]=[CH:11][N:12]=[CH:13][N:14]=2)[C:5](=[O:21])[N:4]2[C:22]3([CH2:29][CH2:30][CH2:31][CH2:32][CH2:27]3)[N:23]([C:35]3[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=3)[C:24](=[O:25])[C:3]=12

Participants

8

Reactant 5

HCID 13181,10-PhenanthrolineHCID 10796Cesium carbonateHCID 707143-IodopyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 118598561HCID 118598561, compound

Product 1

HCID 118598613HCID 118598613, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 8′-chloro-6′-(pyrimidin-4-ylamino)-2′H-spiro[cyclohexane-1,3′-imidazo[1,5-a]pyridine]-1′,5′-dione (1, 450 mg, 1.3 mmol) and 3-iodopyridine (800 mg, 3.9 mmol) in dimethylformamide (10 mL) in a vial, cesium carbonate (550 mg, 1.6 mmol) was added and the mixture was degassed with argon for 15 min. To this mixture 1,10,-phenanthroline (37 mg, 0.2 mmol), copper(I) iodide (12 mg, 0.05 mmol), XantPhos (26 mg, 0.065 mmol) were added and the reaction was heated the mixture at 130° C. for 26 h. TLC showed consumption of starting material, the reaction mixture was filtered over celite bed and washed with 5% methanol in dichloromethane followed by concentration of the filtrate. Obtained solid was purified by Combi-Flash chromatography on neutral alumina using 3% methanol/dichloromethane as a eluent, appropriate fractions were concentrated under reduced pressure to afford 8′-chloro-2′-(pyridin-3-yl)-6′-(pyrimidin-4-ylamino)-2′H-spiro[cyclohexane-1,3′-imidazo[1,5-a]pyridine]-1′,5′-dione (Cpd. No. 136) as yellow solid. Yield: 0.025 g, 4.6%; MS (ESI) m/z 423.12 [M+1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.59 (s, 1H), 8.61 (d, J=2.0 Hz, 1H), 8.58 (s, 1H), 8.49 (d, J=4.8 Hz, 1H), 8.33 (d, J=6.0 Hz, 1H), 8.03 (s, 1H), 7.82 (d, J=8.8 Hz, 1H), 7.47 (dd, J=4.4, 8.8 Hz, 1H), 6.65 (d, J=6.0 Hz, 1H), 2.85-2.79 (m, 2H), 1.74-1.53 (m, 6H), 1.17-1.14 (m, 1H).

Workup

  1. customthe mixture was degassed with argon for 15 min
  2. customconsumption of starting material
  3. filtrationthe reaction mixture was filtered over celite bed
  4. washwashed with 5% methanol in dichloromethane
  5. customObtained solid
  6. customwas purified by Combi-Flash chromatography on neutral alumina using 3% methanol/dichloromethane as a eluent
  7. concentrationappropriate fractions were concentrated under reduced pressure

Sources & evidence

ORD record
ord-0b91aa6a9f4b4bb6b3543282319fb38a
Source dataset
uspto-grants-2016_07
Patent number
US09382248B2

Reaction notes

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