Sodium triacetoxyborohydride → HCID 59605625, compound

HRID 1946009Notes

Reaction equation

HRID 1946009 reaction equation
[CH:1]1([C:4]2[N:8]([C:9]3[N:17]=[C:16]4[C:12]([N:13]=[C:14]([CH:19]=O)[N:15]4[CH3:18])=[C:11]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[N:10]=3)[C:7]3[CH:27]=[CH:28][CH:29]=[CH:30][C:6]=3[N:5]=2)[CH2:3][CH2:2]1.[O:31]1[CH2:36][CH2:35][CH:34]([CH:37]2[CH2:40][NH:39][CH2:38]2)[CH2:33][CH2:32]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH:1]1([C:4]2[N:8]([C:9]3[N:17]=[C:16]4[C:12]([N:13]=[C:14]([CH2:19][N:39]5[CH2:40][CH:37]([CH:34]6[CH2:35][CH2:36][O:31][CH2:32][CH2:33]6)[CH2:38]5)[N:15]4[CH3:18])=[C:11]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[N:10]=3)[C:7]3[CH:27]=[CH:28][CH:29]=[CH:30][C:6]=3[N:5]=2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 177856443-(Oxan-4-yl)azetidineHCID 59605221HCID 59605221, compound

Product 1

HCID 59605625HCID 59605625, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 2-(2-cyclopropylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (100 mg, 0.25 mmol), 3-(tetrahydropyran-4-yl)azetidine (37 mg, 0.26 mmol) and 4 Å powdered molecular sieves (250 mg) in DCE (5 mL) was stirred at room temperature for 5 h before the addition of sodium triacetoxyborohydride (233 mg, 0.92 mmol). The reaction mixture was stirred for 16 h then filtered through celite, washing with DCM. The organic phase was washed with brine (×1) and concentrated in vacuo. The organic phase was dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%). The resulting oil was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH/DCM and the product eluted with 2M NH3/MeOH affording 499 as an orange solid (76 mg, 57%). LCMS (Method I): RT 2.72 min [M+H]+ 529.3. 1H NMR (CDCl3, 400 MHz): δ 7.93 (d, J=7.6 Hz, 1 H); 7.67 (d, J=7.4 Hz, 1 H); 7.27-7.18 (m, 2 H); 4.36 (m, 4 H); 4.00-3.93 (m, 2 H); 3.88-3.83 (m, 9 H); 3.55 (m, 2 H); 3.37 (m, 2 H); 3.06 (m, 2 H); 2.89-2.81 (m, 1 H); 2.34 (m, 1 H); 1.71 (m, 1 H); 1.54 (m, 2 H); 1.38-1.32 (m, 2 H); 1.22 (m, 2 H) and 1.06 (m, 2 H)

Workup

  1. filtrationthen filtered through celite
  2. washwashing with DCM
  3. washThe organic phase was washed with brine (×1)
  4. concentrationconcentrated in vacuo
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%)
  8. washwas washed with MeOH/DCM
  9. washthe product eluted with 2M NH3/MeOH affording 499 as an orange solid (76 mg, 57%)
  10. customRT 2.72 min [M+H]+ 529.3

Sources & evidence

ORD record
ord-ed46f4297a7940298736000557cdc0b3
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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