Triethylamine → tert-Butyl {5-[8-{4-[(dimethylamino)(oxo)acetyl]piperazin-1-yl}-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-yl}carbamate

HRID 1876565Notes

Reaction equation

HRID 1876565 reaction equation
[CH3:1][N:2]([CH3:8])[C:3](=[O:7])[C:4](O)=[O:5].O.OC1C2N=NNC=2C=CC=1.[N:20]1([C:26]2[N:34]=[C:33]([C:35]3[CH:36]=[N:37][C:38]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[N:39][CH:40]=3)[N:32]=[C:31]3[C:27]=2[N:28]=[C:29]([N:54]2[CH2:59][CH2:58][NH:57][CH2:56][CH2:55]2)[N:30]3[CH2:49][C:50]([F:53])([F:52])[F:51])[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>O1CCCC1>[CH3:1][N:2]([C:3](=[O:7])[C:4]([N:57]1[CH2:56][CH2:55][N:54]([C:29]2[N:30]([CH2:49][C:50]([F:51])([F:52])[F:53])[C:31]3[C:27]([N:28]=2)=[C:26]([N:20]2[CH2:21][CH2:22][O:23][CH2:24][CH2:25]2)[N:34]=[C:33]([C:35]2[CH:40]=[N:39][C:38]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[N:37][CH:36]=2)[N:32]=3)[CH2:59][CH2:58]1)=[O:5])[CH3:8]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2760995N,N-Dimethyloxamic acidHCID 59333500tert-Butyl{5-[6-morpholin-4-yl-8-piperazin-1-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-yl}carbamateHCID 178526939HCID 178526939, compound

Product 1

HCID 59333553tert-Butyl {5-[8-{4-[(dimethylamino)(oxo)acetyl]piperazin-1-yl}-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-yl}carbamateYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N,N-Dimethyl-oxalamic acid (34 mg, 0.29 mmol), hydroxybenzotriazole hydrate (45 mg, 0.29 mmol), and tetrahydrofuran (5 ml) were added to tert-butyl {5-[6-morpholin-4-yl-8-piperazin-1-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-yl}carbamate (150 mg, 0.27 mmol). 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (56 mg, 0.29 mmol) and triethylamine (74 μl, 0.53 mmol) were added and the resulting mixture was stirred for 18 hours. The reaction mixture was partitioned with ethyl acetate and water and the organic layer was washed with saturated aqueous sodium bicarbonate solution and dried over magnesium sulfate. The solvent was evaporated under reduced pressure and then the residue was purified by silica gel chromatography (chloroform:methanol=19:1) to give the title compound (148 mg, 84%) as a white solid.

Workup

  1. customThe reaction mixture was partitioned with ethyl acetate and water
  2. washthe organic layer was washed with saturated aqueous sodium bicarbonate solution
  3. dry with materialdried over magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by silica gel chromatography (chloroform:methanol=19:1)

Sources & evidence

ORD record
ord-93612a36486e48af91a8c1d6039ef38a
Source dataset
uspto-grants-2012_11
Patent number
US08309546B2

Reaction notes

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