2-Hydroxyisobutyric acid → HCID 59606046, compound

HRID 1923325Notes

Reaction equation

HRID 1923325 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.[OH:33][C:34]([CH3:39])([CH3:38])[C:35](O)=[O:36].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:35](=[O:36])[C:34]([OH:33])([CH3:39])[CH3:38])[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 116712-Hydroxyisobutyric 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 59606046HCID 59606046, compoundYield 56.5%

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 (60 mg, 0.14 mmol), 2-hydroxyisobutyric acid (17 mg, 0.17 mmol) and DIPEA (29 μL, 0.17 mmol) in DCM (1 mL) was added HATU (63 mg, 0.17 mmol). The resulting yellow mixture was stirred for 1.5 h at r.t. then the reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with DCM and MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-6%) affording 721 as a foam (41 mg, 56%). LCMS (method I): RT 3.00 min, [M+H]+ 519.2. 1H NMR (CDCl3, 400 MHz): δ 8.00-7.97 (1 H, m), 7.75-7.74 (1 H, m), 7.27-7.25 (2 H, m), 4.62 (1 H, s), 4.33 (5 H, s), 4.20 (1 H, s), 3.93 (1 H, s), 3.86 (4 H, t, J=4.72 Hz), 3.76 (3 H, s), 3.64 (1 H, s), 3.34 (3 H, q, J=7.44 Hz), 3.15-3.14 (2 H, m), 1.43-1.42 (9 H, m)

Workup

  1. washwas washed with DCM and MeOH
  2. washthe product eluted with 2M NH3/MeOH
  3. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-6%)

Sources & evidence

ORD record
ord-aa35f0d66db741689480e8956705ec86
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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