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

HRID 1946065Notes

Reaction equation

HRID 1946065 reaction equation
[CH:1]([C:4]1[N:8]([C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([CH:19]=O)[N:15]3[CH3:18])=[C:11]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[N:10]=2)[C:7]2[CH:27]=[CH:28][CH:29]=[CH:30][C:6]=2[N:5]=1)([CH3:3])[CH3:2].[NH:31]1[CH2:34][CH:33]([N:35]2[CH2:40][CH2:39][CH:38]([OH:41])[CH2:37][CH2:36]2)[CH2:32]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH:1]([C:4]1[N:8]([C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([CH2:19][N:31]4[CH2:34][CH:33]([N:35]5[CH2:40][CH2:39][CH:38]([OH:41])[CH2:37][CH2:36]5)[CH2:32]4)[N:15]3[CH3:18])=[C:11]([N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[N:10]=2)[C:7]2[CH:27]=[CH:28][CH:29]=[CH:30][C:6]=2[N:5]=1)([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 220613791-(Azetidin-3-YL)piperidin-4-OLHCID 866482702-(2-isopropylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

Product 1

HCID 596057961-(1-((2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)piperidin-4-olYield 68%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 2-(2-isopropylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (0.150 g, 0.37 mmol), 1-azetidin-3-ylpiperidin-4-ol (0.069 g, 0.44 mmol) and 4 Å molecular sieves (0.37 g) in DCE (3 mL) was stirred for 2 h at room temperature. Sodium triacetoxyborohydride (0.157 g, 0.74 mmol) was added and the reaction mixture was stirred for 4 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 20:80) to give 550 as a white solid (0.137 g, 68%). LCMS (Method I): RT=2.41 min, [M+H]+ 546.3. 1H NMR (400 MHz, DMSO-d6): δ 7.90-7.85 (m, 1 H); 7.66-7.61 (m, 1 H); 7.25-7.21 (m, 2 H); 4.53 (d, J=4.1 Hz, 1 H); 4.28-4.23 (m, 4 H); 3.96-3.86 (m, 1 H); 3.86 (s, 2 H); 3.85-3.68 (m, 7 H); 3.48-3.43 (m, 1 H); 3.42 (t, J=6.5 Hz, 2 H); 2.95 (t, J=6.5 Hz, 2 H); 2.90-2.82 (m, 1 H); 2.45-2.55 (m, 2 H); 1.85 (t, J=10.6 Hz, 2 H); 1.71-1.68 (m, 2 H); 1.40-1.34 (m, 2 H); 1.35 (d, J=6.80 Hz, 6 H)

Workup

  1. stirringthe reaction mixture was stirred for 4 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 20:80)

Sources & evidence

ORD record
ord-98d6b61df0584ba8ac424cd4d303806c
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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