D-Lactic Acid → HCID 59605647, compound

HRID 1923295Notes

Reaction equation

HRID 1923295 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.CN(C=O)C>[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

7

Reactant 4

HCID 61503D-Lactic AcidHCID 81531DiisopropylethylamineHCID 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 59605647HCID 59605647, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 8-azetidin-3-ylmethyl-2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine (57 mg, 0.13 mmol), D-lactic acid (14 mg, 0.16 mmol) and DIPEA (27 μL, 0.16 mmol) in DCM (2 mL) and DMF (1.5 mL) was added HATU (60 mg, 0.16 mmol). The resulting yellow mixture was stirred for 2 h at r.t. then partitioned between DCM and H2O. The combined organic phases were dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-10%) followed by Isolute® SCX-2 cartridge which was washed with MeOH/DCM and the product eluted with 2M NH3/MeOH affording 679 as a cream foam (23 mg, 35%). LCMS: RT 2.92 min, [M+H]+ 505.2. 1H NMR (CDCl3, 400 MHz): δ 8.00-7.98 (1 H, m), 7.81-7.70 (1 H, m), 7.26 (2 H, s), 4.49-4.20 (7 H, m), 3.91 (1 H, dd, J=10.38, 5.67 Hz), 3.86 (5 H, t, J=4.71 Hz), 3.76-3.75 (3 H, m), 3.36-3.35 (4 H, m), 3.18-3.15 (2 H, m), 1.44 (3 H, t, J=7.46 Hz), 1.34 (3 H, dd, J=6.68, 4.79 Hz)

Workup

  1. customthen partitioned between DCM and H2O
  2. dry with materialThe combined organic phases were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-10%)
  5. washwas washed with MeOH/DCM
  6. washthe product eluted with 2M NH3/MeOH affording 679 as a cream foam (23 mg, 35%)

Sources & evidence

ORD record
ord-3e5519a5b7174ddcbfcd0498acd3f4de
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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