Nitrogen → HCID 86697417, compound

HRID 1844328Notes

Reaction equation

HRID 1844328 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][CH2:14][CH3:15])=[N:7][C:6]=12.Cl.[NH2:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22](B(O)[OH:26])=[CH:21][CH:20]=1.[OH2:28].[O-]P([O-])([O-])=O.[K+].[K+].[K+].ClCCl.N#N>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].O>[C:14]([OH:26])(=[O:28])[CH3:15].[NH2:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[CH:9][C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])=[N:7][C:6]=23)=[CH:21][CH:20]=1

Participants

9

Reactant 5

HCID 947Nitrogen2×HCID 6344DichloromethaneHCID 27343114-Aminomethylphenylboronic acid hydrochlorideHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 86697419HCID 86697419, compound

Product 1

HCID 86697417HCID 86697417, compoundYield 31.1%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
85 °C

Procedure

To a mixture of (3-bromo-pyrazolo[1,5-a]pyrimidin-5-yl)-butyl-amine (350.3 mg, 1.3 mmol), 4-aminomethylphenylboronic acid, hydrochloride [75705-21-4] (337.1 mg, 1.8 mmol), potassium phosphate tribasic monohydrate [27176-10-9] (601.6 mg, 2.6 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane [95464-05-4] (117.2 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 (25 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 17 h then cooled and partitioned between brine and ethyl acetate. The phase separated extract was dried (MgSO2) and evaporated to afford a brown oil which was purified by preparative RP-HPLC to yield 71.9 mg of [3-(4-Aminomethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-5-yl]-butyl-amine monoacetate salt as a white solid, mp. 171-172° C. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.97 (t, J=7.39 Hz, 3 H) 1.43 (sxt, J=7.36 Hz, 2 H) 1.64 (quin, J=7.17 Hz, 2 H) 3.43 (q, J=6.47 Hz, 2 H) 3.71-3.84 (m, 2 H) 6.29 (d, J=7.50 Hz, 1 H) 7.34 (m, J=8.16 Hz, 2 H) 7.62-7.71 (m, 1 H) 8.05 (m, J=7.94 Hz, 2 H) 8.32 (s, 1 H) 8.46 (d, J=7.50 Hz, 1 H). 13C NMR (100 MHz, DMSO-d6) δ ppm 13.03, 14.11, 19.63, 29.11, 30.33, 44.34, 45.62, 103.75, 124.02, 124.14, 126.95, 127.86, 131.85, 135.07, 137.50, 141.15, 141.36, 144.46, 155.50, 172.52. LRMS (ESI) m/z 296.1 [(M+H)]+, calc'd for C17H21N5: 295.39.

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. custompartitioned between brine and ethyl acetate
  9. customThe phase separated
  10. extractionextract
  11. dry with materialwas dried (MgSO2)
  12. customevaporated
  13. customto afford a brown oil which
  14. customwas purified by preparative RP-HPLC

Sources & evidence

ORD record
ord-73289934a1054404ae4f7d290083b4fc
Source dataset
uspto-grants-2015_02
Patent number
US08946415B2

Reaction notes

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