Ethylamine → HCID 136247204, compound

HRID 1022445Notes

Reaction equation

HRID 1022445 reaction equation
[CH3:1][N:2]1[C:6]2[N:7]=[C:8]([N:12]3[CH2:17][CH2:16][N:15]([C:18]4[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][CH:19]=4)[CH2:14][CH2:13]3)[NH:9][C:10](=[O:11])[C:5]=2[CH:4]=[CH:3]1.[CH:27]([N:30](CC)C(C)C)(C)[CH3:28].C(N)C.O1CCCC1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>C(Cl)Cl.CO>[CH2:27]([NH:30][C:22](=[O:23])[C:21]1[CH:20]=[CH:19][C:18]([N:15]2[CH2:16][CH2:17][N:12]([C:8]3[NH:9][C:10](=[O:11])[C:5]4[CH:4]=[CH:3][N:2]([CH3:1])[C:6]=4[N:7]=3)[CH2:13][CH2:14]2)=[CH:26][CH:25]=1)[CH3:28]

Participants

9

Reactant 6

HCID 6341EthylamineHCID 8028TetrahydrofuranHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 136344410HCID 136344410, compound

Product 1

HCID 136247204HCID 136247204, compoundYield 9.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 4-(4-(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)piperazin-1-yl)benzoic acid (50.4 mg, 143 μmol) in methylene chloride (1.22 mL) was treated with N,N-diisopropylethylamine (74.1 mg, 100 μL, 570 μmol), a 2M solution of ethylamine in tetrahydrofuran (86 μL, 172 μmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (49.8 mg, 260 μA mol) and 1-hydroxybenzotriazole (28.9 mg, 214 μmol). The resulting white suspension was stirred at room temperature overnight. At this time, the reaction was diluted with methylene chloride (25 mL) and methanol (5 mL), and was washed with a 1N aqueous hydrochloric acid solution (25 mL), a saturated aqueous sodium bicarbonate solution (25 mL), water (25 mL), and a saturated aqueous sodium chloride solution (25 mL). The organic layer was dried over magnesium sulfate and concentrated in vacuo onto Celite®. The product remained in the aqueous layer, so it was extracted with a solution of 10% methanol/methylene chloride (6×25 mL). The combined organics were concentrated in vacuo onto Celite®. Flash chromatography (10 g silica gel column, 1-10% methanol/methylene chloride) afforded N-ethyl-4-[4-(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)-piperazin-1-yl]-benzamide (5.1 mg, 9.4%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.10 (t, J=7.35 Hz, 3H) 3.32 (s, 4H) 3.57 (s, 3H) 3.70 (br. s., 4H) 6.25 (d, J=3.20 Hz, 1H) 6.78 (d, J=3.39 Hz, 1H) 7.00 (d, J=8.67 Hz, 2H) 7.74 (d, J=9.23 Hz, 2H) 8.19 (s, 1H) 10.88 (s, 1H). LC-MS calcd. for C20H25N6O2 [(M+H)+] 381, obsd. 381.1

Workup

  1. washwas washed with a 1N aqueous hydrochloric acid solution (25 mL)
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. concentrationconcentrated in vacuo onto Celite®
  4. extractionwas extracted with a solution of 10% methanol/methylene chloride (6×25 mL)
  5. concentrationThe combined organics were concentrated in vacuo onto Celite®

Sources & evidence

ORD record
ord-adbb0b8564264f61bb2cdc18582dddb8
Source dataset
uspto-grants-2014_05
Patent number
US08722661B2

Reaction notes

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