Sodium triacetoxyborohydride → 1-(1-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)piperidin-4-ol

HRID 1946003Notes

Reaction equation

HRID 1946003 reaction equation
[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH:18]=O)[N:14]3[CH3:17])=[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=2[N:4]=1)[CH3:2].[NH:30]1[CH2:33][CH:32]([N:34]2[CH2:39][CH2:38][CH:37]([OH:40])[CH2:36][CH2:35]2)[CH2:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH2:18][N:30]4[CH2:33][CH:32]([N:34]5[CH2:39][CH2:38][CH:37]([OH:40])[CH2:36][CH2:35]5)[CH2:31]4)[N:14]3[CH3:17])=[C:10]([N:20]3[CH2:21][CH2:22][O:23][CH2:24][CH2:25]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=2[N:4]=1)[CH3:2]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 220613791-(Azetidin-3-YL)piperidin-4-OLHCID 596059872-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

Product 1

HCID 596054441-(1-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)piperidin-4-olYield 55%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (0.167 g, 0.43 mmol), 1-azetidin-3-ylpiperidin-4-ol (0.1 g, 0.64 mmol) and 4 Å molecular sieves (0.8 g) in DCE (8 mL) was stirred for 6 h at room temperature. Sodium triacetoxyborohydride (0.272 g, 1.28 mmol) was added and the reaction mixture was stirred for 18 h at room temperature. The reaction mixture was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 5:95) to give 486 as a yellow solid (0.123 g, 55%). LCMS (Method I): RT=2.31 min, [M+H]+ 532.3. 1H NMR (400 MHz, DMSO-d6): δ 8.03-7.99 (m, 1 H); 7.65-7.61 (m, 1 H); 7.27-7.20 (m, 2 H); 4.54 (d, J=4.0 Hz, 1 H); 4.29-4.22 (m, 4 H); 3.86 (s, 2 H); 3.82-3.73 (m, 7 H); 3.42 (t, J=6.5 Hz, 2 H); 3.30-3.27 (m, 3 H); 3.27 (q, J=7.4 Hz, 2 H); 2.96 (t, J=6.5 Hz, 2 H); 2.89-2.86 (m, 1 H); 1.88-1.85 (m, 2 H); 1.71-1.68 (m, 2 H); 1.39-1.35 (m, 2 H); 1.33 (t, J=7.4 Hz, 3 H)

Workup

  1. stirringthe reaction mixture was stirred for 18 h at room temperature
  2. filtrationThe reaction mixture was filtered through Celite
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 5:95)

Sources & evidence

ORD record
ord-52022308ceb44295addc2ab2bc595a0c
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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