Tetrahydrofuran → HCID 69298926, compound

HRID 131253Notes

Reaction equation

HRID 131253 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]([N:8]([C:14]1[CH:21]=[CH:20][C:17]([CH:18]=O)=[CH:16][CH:15]=1)[CH2:9][CH2:10][N:11]([CH3:13])[CH3:12])=[O:7].O1CCCC1.Cl.Cl.[CH2:29]([O:31][C:32]1[CH:33]=[C:34]([CH:51]=[CH:52][CH:53]=1)[CH2:35][N:36]1[C:40]2=[N:41][CH:42]=[N:43][C:44]([N:45]3[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]3)=[C:39]2[CH:38]=[N:37]1)[CH3:30].C([BH3-])#N>C(O)(=O)C.C(N(CC)CC)C>[CH2:29]([O:31][C:32]1[CH:33]=[C:34]([CH:51]=[CH:52][CH:53]=1)[CH2:35][N:36]1[C:40]2=[N:41][CH:42]=[N:43][C:44]([N:45]3[CH2:46][CH2:47][N:48]([CH2:18][C:17]4[CH:20]=[CH:21][C:14]([N:8]([C:6]([O:5][CH2:4][CH2:3][O:2][CH3:1])=[O:7])[CH2:9][CH2:10][N:11]([CH3:13])[CH3:12])=[CH:15][CH:16]=4)[CH2:49][CH2:50]3)=[C:39]2[CH:38]=[N:37]1)[CH3:30]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 498716Cyano-borohydrideHCID 69298924HCID 69298924, compoundHCID 86605583HCID 86605583, compound

Product 1

HCID 69298926HCID 69298926, compoundYield 106%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8471TriethylamineSolvent

Procedure

To 4-[N-[(2-methoxyethoxy)carbonyl]-N-[2-(dimethylamino)ethyl]amino]-benzaldehyde (90 mg, compound obtained in Reference Example 97) is added successively tetrahydrofuran (1.5 mL), 1-(3-ethoxybenzyl)-4-(1-piperazinyl)-1H-pyrazolo[3,4-d]pyrimidine dihydrochloride (100 mg), triethylamine (90 μL), acetic acid (73 μL) and macroporous triethylammoniummethylpolystylenecyanoborohydride (MP-Cyanoborohydride 2.04 mmol/g, Argonaut Technology). The mixture is shaken at room temperature for 18 hours by using a parallel synthesizer (MiniBlock; Mettler Toledo). The reaction mixture is separated and the residual resin is washed with tetrahydrofuran (×3). The washings and the reaction solution are combined and concentrated. The resultant crude product is purified by flash column chromatography on silica gel (Solvent; ethyl acetate:chloroform=1:0→0:1) to give 1-(3-ethoxybenzyl)-4-[4-[4-[N-[(2-methoxyethoxy)carbonyl]-N-[2-(dimethylamino)ethyl]-amino]benzyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine (159 mg, yield; 38%) as an amorphous powder. MS (APCI) m/z: 617 [M+H]+

Workup

  1. customThe reaction mixture is separated
  2. washthe residual resin is washed with tetrahydrofuran (×3)
  3. concentrationconcentrated
  4. customThe resultant crude product is purified by flash column chromatography on silica gel (Solvent; ethyl acetate:chloroform=1:0→0:1)

Sources & evidence

ORD record
ord-eb2ff38ffdaa48ca8a5ecdf960fcad81
Source dataset
uspto-grants-2008_06
Patent number
US07384952B2

Reaction notes

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