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 421375Notes

Reaction equation

HRID 421375 reaction equation
[CH3:1][N:2]([CH3:8])[C:3](=[O:7])[C:4](O)=[O:5].O.OC1C2N=NNC=2C=CC=1.[C:20]([O:24][C:25](=[O:59])[NH:26][C:27]1[N:32]=[CH:31][C:30]([C:33]2[N:41]=[C:40]3[C:36]([N:37]=[C:38]([N:47]4[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]4)[N:39]3[CH2:42][C:43]([F:46])([F:45])[F:44])=[C:35]([N:53]3[CH2:58][CH2:57][O:56][CH2:55][CH2:54]3)[N:34]=2)=[CH:29][N:28]=1)([CH3:23])([CH3:22])[CH3:21].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:50]1[CH2:49][CH2:48][N:47]([C:38]2[N:39]([CH2:42][C:43]([F:45])([F:46])[F:44])[C:40]3[C:36]([N:37]=2)=[C:35]([N:53]2[CH2:58][CH2:57][O:56][CH2:55][CH2:54]2)[N:34]=[C:33]([C:30]2[CH:31]=[N:32][C:27]([NH:26][C:25](=[O:59])[O:24][C:20]([CH3:23])([CH3:21])[CH3:22])=[N:28][CH:29]=2)[N:41]=3)[CH2:52][CH2:51]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-a2aaf61aefb144bd9c5ee2247e46db3f
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Reaction notes

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