Nitrogen → HCID 178495865, compound

HRID 1844331Notes

Reaction equation

HRID 1844331 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([NH:11][CH2:12][CH2:13][O:14][CH3:15])=[N:7][C:6]=12.[NH:16]1[C:20]([C:21]2[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=2)=[N:19][N:18]=[N:17]1.O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].ClCCl.N#N>COCCOC.CO.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].O>[CH3:15][O:14][CH2:13][CH2:12][NH:11][C:8]1[CH:9]=[CH:10][N:5]2[N:4]=[CH:3][C:2]([C:24]3[CH:23]=[CH:22][C:21]([C:20]4[NH:19][N:18]=[N:17][N:16]=4)=[CH:26][CH:25]=3)=[C:6]2[N:7]=1

Participants

10

Reactant 5

HCID 947Nitrogen2×HCID 6344DichloromethaneHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 86697422HCID 86697422, compoundHCID 178514828HCID 178514828, compound

Product 1

HCID 178495865HCID 178495865, compound

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of (3-bromo-pyrazolo[1,5-a]pyrimidin-5-yl)-(2-methoxy-ethyl)-amine (307.7 mg, 1.1 mmol), (4-(1H-tetrazol-5-yl)phenyl)boronic acid [179942-55-3] (259.6 mg, 1.4 mmol), potassium phosphate tribasic monohydrate [27176-10-9] (522.4 mg, 2.3 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloro-palladium(II), complex with dichloromethane [95464-05-4] (106.3 mg, 0.1 mmol) contained in a 50 mL round bottomed flask was added a solution of 30% (v/v) water in 1,2-dimethoxyethane (12 mL) and a magnetic stir bar. The reaction pot was fitted to a reflux condenser, lowered into an ambient temperature oil bath, and the system taken through 10 evacuation/N2 blanket cycles while being rapidly stirred. The rapidly stirred, N2 blanketed, reaction was heated to an oil bath temperature of 85° C. for 4 h then cooled, diluted with methanol, and gravity filtered. The filtrate was preabsorbed on silica gel and flash chromatographed (silica gel eluted with 1% NH4OH in 10% (v/v) methanol/ethyl acetate). Desired chromatography fractions were combined, evaporated, redissolved in 2-propanol and gravity filtered into stirring heptane to precipitate purified product. (2-Methoxy-ethyl)-{3-[4-(1H-tetrazol-5-yl)-phenyl]-pyrazolo[1,5-a]pyrimidin-5-yl}-amine was isolated by filtration as 96.3 mg of solid material, mp. 264-265° C. (dec.). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.63 (t, J=4.29 Hz, 5 H) 6.41 (d, J=7.58 Hz, 1 H) 7.88 (br. s., 1 H) 8.04 (m, J=8.59 Hz, 2 H) 8.31 (m, J=8.34 Hz, 2 H) 8.47 (s, 1 H) 8.53 (d, J=7.58 Hz, 1 H). 13C NMR (100 MHz, DMSO-d6) δ ppm 40.69, 58.48, 70.48, 100.86, 103.75, 119.86, 125.23, 127.61, 135.97, 137.08, 142.42, 145.63, 156.60, LRMS (ESI) m/z 337.2 [(M+H)]+, calc'd for C16H16N8O: 336.36.

Workup

  1. customcontained in a 50 mL round bottomed flask
  2. customThe reaction
  3. custompot was fitted to a reflux condenser
  4. customlowered into an ambient temperature
  5. stirringThe rapidly stirred
  6. customreaction
  7. temperaturethen cooled
  8. filtrationfiltered
  9. customThe filtrate was preabsorbed on silica gel and flash
  10. customchromatographed
  11. wash(silica gel eluted with 1% NH4OH in 10% (v/v) methanol/ethyl acetate)
  12. customevaporated
  13. dissolutionredissolved in 2-propanol
  14. filtrationgravity filtered
  15. stirringinto stirring heptane
  16. customto precipitate
  17. custompurified product

Sources & evidence

ORD record
ord-046468f3edfe4d37bd2d7aa9d6ed269a
Source dataset
uspto-grants-2015_02
Patent number
US08946415B2

Reaction notes

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