Water → HCID 58269207, compound

HRID 1476254Notes

Reaction equation

HRID 1476254 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16]4[C:21]([C:22](=[O:31])[C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH3:13])[N:9]=[C:10](I)[C:3]=12.O.[CH3:33][O:34][C:35]1[CH:36]=[C:37](B(O)O)[CH:38]=[C:39]([O:41][CH3:42])[CH:40]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16]4[C:21]([C:22](=[O:31])[C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH3:13])[N:9]=[C:10]([C:37]3[CH:36]=[C:35]([O:34][CH3:33])[CH:40]=[C:39]([O:41][CH3:42])[CH:38]=3)[C:3]=12

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 4374257(3,5-Dimethoxyphenyl)boronic acidHCID 665799322-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-(3-fluorophenyl)-4H-chromen-4-one

Product 1

HCID 58269207HCID 58269207, compound

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of example 57c (100 mg, 0.190 mmol) in DME (1 ml), and water (0.5 ml), 3,5-dimethoxy phenyl boronic acid (0.209 mmol) and sodium carbonate (40 mg, 0.380 mmol) were added and the system was degassed for 5 min 1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (27.8 mg, 0.038 mmol) was added under nitrogen atmosphere and the mixture was heated to 90° C. at a microwave reactor for 15 min LC-MS analysis indicated the total consumption of example 57c, then ethyl acetate (2 ml) and water (0.5 ml) was added. The two phases were separated and the aqueous layer was extracted by ethyl acetate (1 ml). The combined organic layer was dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by preparative TLC using mixture of ethyl acetate: petroleum ether in 2:1 ratio as an eluent to afford the desired compound. Brown solid (23.4 mg, 23%). MP: 224-227° C. 1H-NMR (δ ppm, CDCl3, 300 MHz): δ 8.24(s,1H), 8.21(dd, J=8.0,1.5 Hz, 1H), 7.69(m,1H), 7.48(d, J=8.4 Hz, 1H), 7.42(t, J=8.0 Hz, 1H), 7.32(m,1H), 7.04(m,3H), 6.79(d, J=2.3 Hz, 2H), 6.56(t, J=2.1 Hz, 1H), 6.11(q, J=7.2 Hz, 1H), 5.58(s,2H), 3.85(s, 6H), 2.02(d, J=7.1 Hz, 3H). Mass: 537.8(M+).

Workup

  1. additionwas added under nitrogen atmosphere
  2. customthe total consumption of example 57c
  3. additionethyl acetate (2 ml) and water (0.5 ml) was added
  4. customThe two phases were separated
  5. extractionthe aqueous layer was extracted by ethyl acetate (1 ml)
  6. dry with materialThe combined organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customThe residue was purified by preparative TLC
  10. additionmixture of ethyl acetate

Sources & evidence

ORD record
ord-69d59cc69ea9422abb1a574b93a3cc1a
Source dataset
uspto-grants-2015_04
Patent number
US09018375B2

Reaction notes

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