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

HRID 1923283Notes

Reaction equation

HRID 1923283 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[CH2:38][CH2:37][C:36]([F:40])([F:39])[CH2:35]2)[CH2:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[F:40][C:36]1([F:39])[CH2:37][CH2:38][N:34]([CH:32]2[CH2:33][N:30]([CH2:18][C:13]3[N:14]([CH3:17])[C:15]4[C:11]([N:12]=3)=[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:9]=[C:8]([N:7]3[C:6]5[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=5[N:4]=[C:3]3[CH2:1][CH3:2])[N:16]=4)[CH2:31]2)[CH2:35]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 596053851-(Azetidin-3-yl)-3,3-difluoropyrrolidineHCID 596059872-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

Product 1

HCID 596061074-(8-((3-(3,3-difluoropyrrolidin-1-yl)azetidin-1-yl)methyl)-2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-9H-purin-6-yl)morpholineYield 69.4%

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 (100 mg, 0.26 mmol), 1-azetidin-3-yl-3,3-difluoropyrrolidine (46 mg, 0.28 mmol) and 4 Å powdered molecular sieves in DCE (6 mL) was stirred at room temperature for 2 h before the addition of sodium triacetoxyborohydride (108 mg, 0.52 mmol). The reaction mixture was stirred for 16 h then filtered through celite, washing with DCM. The organic phase was washed with brine 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:EtOAc, 0-10%) affording 589 as an orange foam (97 mg, 69%). LCMS (method I): RT 2.74 min [M+H]+ 538.2 1H NMR (CDC3, 300 MHz): δ 8.00 (m, 1 H), 7.75 (m, 1 H), 7.27 (m, 2 H), 4.42-4.27 (m, 4 H), 3.87-3.84 (m, 9 H), 3.54 (t, J=6.5 Hz, 2 H), 3.32-3.30 (m, 3 H), 3.19 (t, J=6.5 Hz, 2 H), 2.89 (t, J=13.1 Hz, 2 H), 2.70 (t, J=6.9 Hz, 2 H), 2.29-2.28 (m, 2 H) and 1.44 (t, J=7.5 Hz, 3 H)

Workup

  1. filtrationthen filtered through celite
  2. washwashing with DCM
  3. washThe organic phase was washed with brine
  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:EtOAc, 0-10%)

Sources & evidence

ORD record
ord-80090c3c691c43ab921a19e5e47a77b9
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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