Methanol → HCID 68425418, compound

HRID 1802496Notes

Reaction equation

HRID 1802496 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[C:4]([Cl:9])[C:3]=1[NH:10][C:11]1[C:20]2[CH:21]=[CH:22][N:23]=[C:24]([O:25][CH2:26][CH3:27])[C:19]=2[C:18]2[C:13](=[CH:14][CH:15]=[N:16][CH:17]=2)[N:12]=1.[Cl:28][C:29]1[CH:34]=[C:33](I)[CH:32]=[C:31]([Cl:36])[C:30]=1[NH:37][C:38]1[C:47]2[CH:48]=[CH:49][N:50]=[C:51]([O:52][CH3:53])[C:46]=2[C:45]2[C:40](=[CH:41][CH:42]=[N:43][CH:44]=2)[N:39]=1.CN(C1C=CC=CN=1)C.C(N(C(C)C)CC)(C)C.[CH3:72][OH:73]>[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([Cl:9])[C:3]=1[NH:10][C:11]1[C:20]2[CH:21]=[CH:22][N:23]=[C:24]([O:25][CH2:26][CH3:27])[C:19]=2[C:18]2[C:13](=[CH:14][CH:15]=[N:16][CH:17]=2)[N:12]=1)[C:51]([O:52][CH3:53])=[O:73].[Cl:28][C:29]1[CH:34]=[C:33]([CH:32]=[C:31]([Cl:36])[C:30]=1[NH:37][C:38]1[C:47]2[CH:48]=[CH:49][N:50]=[C:51]([O:52][CH3:53])[C:46]=2[C:45]2[C:40](=[CH:41][CH:42]=[N:43][CH:44]=2)[N:39]=1)[C:72]([O:25][CH3:24])=[O:73]

Participants

9

Reactant 5

HCID 887MethanolHCID 218852-DimethylaminopyridineHCID 81531DiisopropylethylamineHCID 59436020HCID 59436020, compoundHCID 59436035HCID 59436035, compound

Product 2

HCID 68425418HCID 68425418, compoundHCID 68668103HCID 68668103, compound

Reagents, catalysts & solvents 2

HCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
150 °C

Procedure

The carbonylation reaction was conducted following the procedure described in J. Comb. 2003, 5, 350. To a solution of N-(2,6-dichloro-4-iodophenyl)-10-ethoxypyrido[4,3-c]-1,6-naphthyridin-6-amine (Example 152, Step 1) (130 mg, 0.39 mmol) and N-(2,6-dichloro-4-iodophenyl)-10-methoxypyrido[4,3-c]-1,6-naphthyridin-6-amine (Example 152, Step 1) (66 mg, 0.13 mol) in methanol (5 mL) were added dimethylamino pyridine (96 mg, 0.78 mmol), diisopropylethylamine (137 uL, 0.78 mmol), molybdenumhexacarbonyl (106 mg, 0.39 mmol) and palladium (II) acetate (9 mg, 0.39 mmol). The solution was heated in a microwave reactor at 150° C. for 15 min. The black solution was extracted with EtOAc and water, dried with MgSO4, filtered, and concentrated under reduced pressure. Purification by chromatography on silica gel (100% hexanes to 100% EtOAc) afforded methyl 3,5-dichloro-4-[(10-ethoxypyrido[4,3-c]-1,6-naphthyridin-6-yl)amino]benzoate and methyl 3,5-dichloro-4-[(10-methoxypyrido[4,3-c]-1,6-naphthyridin-6-yl)amino]benzoate. The mixture of esters (117 mg, 0.27 mmol) were suspended in CHCl3 (5 mL) followed by addition of BBr3 (1.91 mL, 1.91 mmol). The reaction mixture was heated to 85° C. for 45 min. After cooling to room temperature, the solution was extracted with EtOAc and saturated NaHCO3, dried with MgSO4, filtered, and concentrated. Purification by chromatography on silica gel (100% CH2Cl2 to 70% CH2Cl2/30% MeOH) afforded the title compound.

Workup

  1. customThe carbonylation reaction
  2. extractionThe black solution was extracted with EtOAc and water
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by chromatography on silica gel (100% hexanes to 100% EtOAc)

Sources & evidence

ORD record
ord-e43411c6437147b482ddcde2eb8ca0d4
Source dataset
uspto-grants-2013_01
Patent number
US08349865B2

Reaction notes

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