Sodium triacetoxyborohydride → 2-Chloro-9-methyl-6-morpholin-4-yl-8-[4-(tetrahydropyran-4-yl)piperazin-1-ylmethyl]-9H-purine

HRID 1922826Notes

Reaction equation

HRID 1922826 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:12]=O)[N:8]2[CH3:11])=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:3]=1.[O:20]1[CH2:25][CH2:24][CH:23]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH2:22][CH2:21]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][N:29]3[CH2:28][CH2:27][N:26]([CH:23]4[CH2:24][CH2:25][O:20][CH2:21][CH2:22]4)[CH2:31][CH2:30]3)[N:8]2[CH3:11])=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:3]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 219423151-(Oxan-4-yl)piperazineHCID 596034722-Chloro-9-methyl-6-morpholino-9H-purine-8-carbaldehyde

Product 1

HCID 596055882-Chloro-9-methyl-6-morpholin-4-yl-8-[4-(tetrahydropyran-4-yl)piperazin-1-ylmethyl]-9H-purineYield 98%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 2-chloro-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (165 mg, 0.59 mmol), 1-(tetrahydropyran-4-yl)piperazine (110 mg, 0.65 mmol) and molecular sieves (4 Å, powdered, 750 mg) in DCE (10 mL) was stirred at ambient temperature for 4 h. Sodium triacetoxyborohydride (170 mg, 0.80 mmol) was added and the mixture stirred for 18 h, then loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH, 100:0 to 98:2 to 95:5 to 90:10) to afford 2-Chloro-9-methyl-6-morpholin-4-yl-8-[4-(tetrahydropyran-4-yl)piperazin-1-ylmethyl]-9H-purine as a white solid (250 mg, 98%). 1H NMR (CDCl3, 400MHz) δ 4.27 (m, 4 H), 4.01 (dd, J=11.5, 4.2 Hz, 2 H), 3.81 (m, 7 H), 3.69 (s, 2 H), 3.36 (dd, J=12.5, 10.9 Hz, 2 H), 2.55 (m, 8 H), 2.40 (m, 1 H), 1.75 (d, J=12.5 Hz, 2 H) and 1.56 (m, 2 H)

Workup

  1. stirringthe mixture stirred for 18 h
  2. washThe cartridge was then washed with methanol
  3. washthe desired product was subsequently eluted
  4. customThe product was collected
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH, 100:0 to 98:2 to 95:5 to 90:10)

Sources & evidence

ORD record
ord-8733b57954bb4d6db99eeeaee973de70
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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