Sodium Carbonate → HCID 68519649, compound

HRID 1171024Notes

Reaction equation

HRID 1171024 reaction equation
I[C:2]1[C:6]2[N:7]=[CH:8][N:9]=[C:10]([NH2:11])[C:5]=2[N:4]([C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[C:14]([O:21][CH3:22])[CH:13]=2)[N:3]=1.CC1(C)C(C)(C)OB([C:31]2[CH2:32][CH2:33][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:35][CH:36]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:11][C:10]1[C:5]2[N:4]([C:12]3[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[C:14]([O:21][CH3:22])[CH:13]=3)[N:3]=[C:2]([C:31]3[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH:32]=3)[C:6]=2[N:7]=[CH:8][N:9]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate2×HCID 685196943-Iodo-1-(3-methoxy-4-nitrophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

Product 1

HCID 68519649HCID 68519649, compoundYield 60.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 3-iodo-1-(3-methoxy-4-nitrophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine (300 mg, 0.728 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydro-1-pyridinecarboxylate (270 mg, 0.874 mmol), sodium carbonate (185 mg, 1.75 mmol) and tetrakis(triphenylphosphine)palladium(0) (50 mg, 0.044 mmol) in 1,2-dimethoxy ethane (6 mL) and water (3 mL) was heated in an 85° C. oil bath for 1.75 hours. tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydro-1-pyridinecarboxylate (45 mg, 0.146 mmol) was added to the mixture and then it was heated in the 85° C. oil bath for another 16 hours. The solvents were evaporated under reduced pressure then the residue was partitioned between water (10 mL) and ethyl acetate (15 mL). The layers were separated and then the aqueous layer was extracted with ethyl acetate (10 mL), dichloromethane (20 mL) and then a 10% solution of methanol in dichloromethane (20 mL). The organic solutions thus obtained were combined and evaporated to a residue which was purified by flash chromatography on silica gel using ethyl acetate as an eluent to provide the title compound as a yellow solid (205 mg, 60%): 1H NMR (DMSO-d6, 400 MHz) δ 8.40 (s, 1H), 8.10 (d, 1H), 7.50 (m, 1H), 7.42 (s, 1H), 7.31 (d, 1H), 7.1 (bs, 2H), 4.13 (m, 2H), 3.99 (s, 3H), 3.58 (m, 2H), 2.67 (m, 2H), 1.44 (s, 9H) RP-HPLC (Hypersil HS C18, 5 μm, 100 A, 250×4.6 mm; 5%-100% acetonitrile-0.05 M ammonium acetate over 25 min, 1 mL/min) tr 21.42 min; MS: M−H+ 466.3

Workup

  1. temperatureit was heated in the 85° C. oil bath for another 16 hours
  2. customThe solvents were evaporated under reduced pressure
  3. customthe residue was partitioned between water (10 mL) and ethyl acetate (15 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (10 mL), dichloromethane (20 mL)
  6. customThe organic solutions thus obtained
  7. customevaporated to a residue which
  8. customwas purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-bbf7761bb2f248ca9a21ec6cdf27aeca
Source dataset
uspto-grants-2010_11
Patent number
US07829570B2

Reaction notes

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