Diisopropylethylamine → HCID 59605980, compound

HRID 1923323Notes

Reaction equation

HRID 1923323 reaction equation
[NH:1]1[CH2:4][CH:3]([CH2:5][C:6]2[N:7]([CH3:32])[C:8]3[C:13]([N:14]=2)=[C:12]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:11]=[C:10]([N:21]2[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=4[N:23]=[C:22]2[CH2:30][CH3:31])[N:9]=3)[CH2:2]1.[C:33](O)(=[O:37])[C@H:34]([CH3:36])[OH:35].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[CH2:30]([C:22]1[N:21]([C:10]2[N:9]=[C:8]3[C:13]([N:14]=[C:6]([CH2:5][CH:3]4[CH2:2][N:1]([C:33](=[O:37])[C@@H:34]([OH:35])[CH3:36])[CH2:4]4)[N:7]3[CH3:32])=[C:12]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[N:11]=2)[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[N:23]=1)[CH3:31]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 107689L-Lactic AcidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 596052818-Azetidin-3-ylmethyl-2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine

Product 1

HCID 59605980HCID 59605980, compoundYield 16.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 8-azetidin-3-ylmethyl-2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine (100 mg, 0.23 mmol), L-lactic acid (23 mg, 0.25 mmol) and DIPEA (45 μL, 0.25 mmol) in DCM (2 mL) was added HATU (96 mg, 0.25 mmol). The resulting yellow mixture was stirred for 2.5 h at r.t. then partitioned between DCM and H2O. The combined organic phases were dried (Na2SO4) and concentrated in vacuo. 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. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-10%) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient acetonitrile 20-35%) affording 718 as a white solid (19 mg, 16%). LCMS (method I): RT 2.92 min, [M+H]+ 505.2. 1H NMR (CDCl3, 400 MHz): δ 7.98-7.97 (1 H, m), 7.90-7.80 (1 H, m), 7.40-7.30 (2 H, m), 4.33-4.32 (7 H, m), 4.01-4.00 (1 H, m), 3.86-3.85 (5 H, m), 3.77 (3 H, d, J=1.96 Hz), 3.50-3.35 (4 H, m), 3.19-3.17 (2 H, m), 1.48 (3 H, t, J=7.42 Hz), 1.34 (3 H, dd, J=6.69, 4.73 Hz),

Workup

  1. customthen partitioned between DCM and H2O
  2. dry with materialThe combined organic phases were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. washwas washed with MeOH/DCM
  5. washthe product eluted with 2M NH3/MeOH
  6. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-10%)

Sources & evidence

ORD record
ord-13a499c5e5f04903b92cdf0b18798c21
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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