Dichloromethane → HCID 46941216, compound

HRID 2409598Notes

Reaction equation

HRID 2409598 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[C:4]([NH2:18])=[N:5][CH:6]=[C:7]([C:9]2[S:13][C:12]3=[N:14][CH:15]=[C:16](I)[N:11]3[N:10]=2)[CH:8]=1.[CH3:21][O:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][C:28]=1[C:29]([O:31][CH3:32])=[O:30].C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:32][O:31][C:29](=[O:30])[C:28]1[CH:27]=[CH:26][C:25]([C:16]2[N:11]3[C:12]([S:13][C:9]([C:7]4[CH:6]=[N:5][C:4]([NH2:18])=[C:3]([C:2]([F:20])([F:19])[F:1])[CH:8]=4)=[N:10]3)=[N:14][CH:15]=2)=[CH:24][C:23]=1[O:22][CH3:21]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 177502563-Methoxy-4-(methoxycarbonyl)benzeneboronic acidHCID 66716934HCID 66716934, compound

Product 1

HCID 46941216HCID 46941216, compoundYield 0.9%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of 3-(trifluoromethyl)-5-(5-iodoimidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyridin-2-amine (0.500 g, 1.216 mmol, 1 eq), 3-methoxy-4-methoxycarbonylphenylboronic acid (0.306 g, 1.459 mmol, 1.2 eq), Pd(dppf)Cl2.DCM (0.105 g, 0.126 mmol, 0.1 eq) in DME was added a sat. aq. solution of Na2CO3 (2 mL). The reaction mixture was heated in a sealed tube at 90° C. over the weekend. The solid was filtered off, washed with MeOH and treated with a mixture of DCM and MeOH. The solid was removed by filtration, and the filtrate was evaporated to dryness to give the desired product (0.005 g). HPLC-MS (5-100% B in 8 min at 0.8 mL): tR=5.50 min, [M+H]+ m/z 450.1; 1H NMR (300 MHz, DMSO) δ=8.82 (d, J=1.8, 1H), 8.24 (s, 1H), 8.01 (s, 1H), 7.87 (s, 1H), 7.80 (d, J=8.1, 1H), 7.71 (d, J=8.2, 1H), 7.42 (br s, 2H), 3.95 (s, 3H), 3.80 (s, 3H) ppm.

Workup

  1. filtrationThe solid was filtered off
  2. washwashed with MeOH
  3. additiontreated with a mixture of DCM and MeOH
  4. customThe solid was removed by filtration
  5. customthe filtrate was evaporated to dryness

Sources & evidence

ORD record
ord-b1e359f91f27424d840b3e62b00f6258
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

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