Potassium Hydroxide → 4-[3-[4-[Bis(4-fluorophenyl)methyl]-piperazin-1-yl]-2-hydroxy-propoxy]-1-(tetrahydropyran-2-yl)pyrazolo[3,4-d]pyrimidine

HRID 359386Notes

Reaction equation

HRID 359386 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH:16]([OH:19])[CH2:17][OH:18])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.Cl[C:28]1[N:33]=[CH:32][N:31]=[C:30]2[N:34]([CH:37]3[CH2:42][CH2:41][CH2:40][CH2:39][O:38]3)[N:35]=[CH:36][C:29]=12.[OH-].[K+].C1OCCOCCOCCOCCOCCOC1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)[N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH:16]([OH:19])[CH2:17][O:18][C:28]3[N:33]=[CH:32][N:31]=[C:30]4[N:34]([CH:37]5[CH2:42][CH2:41][CH2:40][CH2:39][O:38]5)[N:35]=[CH:36][C:29]=34)[CH2:11][CH2:10]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 14797Potassium HydroxideHCID 2855718-Crown-6HCID 2394984-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidineHCID 104063373-[4-[Bis(4-fluorophenyl)methyl]-1-piperazinyl]-1,2-propanediol

Product 1

HCID 156708664-[3-[4-[Bis(4-fluorophenyl)methyl]-piperazin-1-yl]-2-hydroxy-propoxy]-1-(tetrahydropyran-2-yl)pyrazolo[3,4-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A toluene solution (30 mL) of 3-[4-[bis(4-fluorophenyl) methyl]-1-piperazinyl]-1,2-propanediol (3.98 g, 11 mmol) was added dropwise to a stirred mixture of 4-chloro-1-(tetrahydropyran-2-yl)-pyrazolo[3,4-d]pyrimidine (2.387 g, 10 mmol), powdered KOH (0.485 g, 8.51 mmol), 18-crown-6 (3, 90.2 mg, 0.34 mmol) in toluene (70 mL) over a 20 min period. The mixture was stirred at room temperature for 3 h and washed with water (3×70 mL). The organic layer was dried (Na2SO4), filtered and evaporated to dryness. The oily residue (7.0 g) was purified on a medium pressure silica gel column eluting with increasing proportions of methanol in methylene chloride. The title compound was obtained as the major product (1.49 g, 41%), mp 101°-105° C. IR (KBr) cm-1 : 2466, 2446, 2401, 1603, 1568, 1506, 1347, 1222. 1H NMR (CDCl3) δ: 8.35 (s, 1H, 3 or 6-H), 8.12 (s, 1H, 3 or 6-H), 6.9-7.4 (m, 8H, Ar--H), 5.0 (m, 1H, N--O--CH--C), 4.6 (m, 2H, OCH2), 4.23 [s, 1H, CH(O)2 ], 4.15 (m, 2H, HCOH, O--CHN), 3.8 (m, 1H, OCNH), 1.6-2.9 (m, 16H, CH2, NCH2 ; MS(DCI): 565 (MH)+.

Workup

  1. washwashed with water (3×70 mL)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customThe oily residue (7.0 g) was purified on a medium pressure silica gel column
  6. washeluting with increasing proportions of methanol in methylene chloride

Sources & evidence

ORD record
ord-29a70c5faf2b45758e80d0552e187837
Source dataset
uspto-grants-1991_03
Patent number
US05001127

Reaction notes

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