Diisopropylethylamine → HCID 59605462, compound

HRID 1923359Notes

Reaction equation

HRID 1923359 reaction equation
[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([C:18](O)=[O:19])[N:14]3[CH3:17])=[C:10]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[N:9]=2)[C:6]2[CH:27]=[CH:28][CH:29]=[CH:30][C:5]=2[N:4]=1)[CH3:2].[I-].ClC1C=CC=C[N+]=1C.CCN(C(C)C)C(C)C.[NH:49]1[CH2:52][CH:51]([N:53]2[CH2:58][CH2:57][CH:56]([OH:59])[CH2:55][CH2:54]2)[CH2:50]1>CN(C=O)C>[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([C:18]([N:49]4[CH2:52][CH:51]([N:53]5[CH2:58][CH2:57][CH:56]([OH:59])[CH2:55][CH2:54]5)[CH2:50]4)=[O:19])[N:14]3[CH3:17])=[C:10]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[N:9]=2)[C:6]2[CH:27]=[CH:28][CH:29]=[CH:30][C:5]=2[N:4]=1)[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1670692-Chloro-1-methylpyridinium iodideHCID 220613791-(Azetidin-3-YL)piperidin-4-OLHCID 596053252-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purine-8-carboxylic acid

Product 1

HCID 59605462HCID 59605462, compoundYield 26.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carboxylic acid (215 mg, 0.53 mmol), 2-chloro-1-methylpyridinium iodide (324 mg, 1.27 mmol) and DIPEA (460 μL, 2.64 mmol) in DMF (2 mL) was stirred for 5 min before the addition of 1-azetidin-3-ylpiperidin-4-ol (140 mg, 0.90 mmol) in DMF (2 mL). The resulting mixture was allowed to stir for 2 h then loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si-PCC, MeOH:DCM, 0-10%) affording 797 as a pale yellow solid (76 mg, 26%). LCMS (method G): RT 5.26 min, [M+H]+ 546.4. 1H NMR (CDCl3, 400 MHz): δ 8.06-8.06 (1 H, m), 7.76-7.75 (1 H, m), 7.31-7.24 (2 H, m), 4.72-4.71 (1 H, m), 4.50 (1 H, dd, J=10.65, 5.40 Hz), 4.30-4.20 (1 H, m), 4.14 (3 H, s), 4.14-4.07 (1 H, m), 3.88 (4 H, t, J=4.71 Hz), 3.81 (1 H, s), 3.37 (2 H, q, J=7.47 Hz), 3.28-3.27 (1 H, m), 2.72 (2 H, d, J=27.26 Hz), 2.25-2.10 (2 H, m), 2.01-1.91 (2 H, m), 1.68-1.60 (5 H, m), 1.46-1.43 (4 H, m)

Workup

  1. washwas washed with MeOH
  2. washthe product eluted with 2M NH3/MeOH
  3. customThe resulting residue was purified by column chromatography (Si-PCC, MeOH:DCM, 0-10%)

Sources & evidence

ORD record
ord-5c8bc18d8cc044ce8bed34044ebae579
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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