Diisopropylethylamine → HCID 178484318, compound

HRID 473580Notes

Reaction equation

HRID 473580 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]([CH3:23])[CH2:5][C@H:6]1[O:10][C@@H:9]([N:11]2[C:20]3[N:19]=[CH:18][N:17]=[C:15]([NH2:16])[C:14]=3[N:13]=[CH:12]2)[C@H:8]([OH:21])[C@@H:7]1[OH:22].[N:24]1([C:29](N)=[NH:30])C=CC=N1.CCN(C(C)C)C(C)C>CN(C=O)C>[NH:1]([CH2:2][CH2:3][N:4]([CH3:23])[CH2:5][C@H:6]1[O:10][C@@H:9]([N:11]2[C:20]3[N:19]=[CH:18][N:17]=[C:15]([NH2:16])[C:14]=3[N:13]=[CH:12]2)[C@H:8]([OH:21])[C@@H:7]1[OH:22])[C:29]([NH2:30])=[NH:24]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2734673PraxadineHCID 25233590(2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-{[(2-aminoethyl)(methyl)amino]methyl}oxolane-3,4-diol

Product 1

HCID 178484318HCID 178484318, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 14e (218 mg, 0.67 mmol) and 1H-pyrazole-1-carboxamidine hydrochloride50 (196 mg, 1.34 mmol) in anhydrous DMF (5 mL) was added DIEA (479 mg, 0.65 mL, 3.7 mmol) under nitrogen at 5° C. Stirring was continued at room temperature overnight. The reaction mixture was concentrated to dryness and the product was purified by column chromatography (silica gel 230-400 mesh, elution with 4:1:0.3 chloroform:methanol:NH4OH). The desired fractions were combined, concentrated, and dried in vacuo to give a white solid: yield 219 mg (89%), MS: m/z 366 (M+H)+; 1HNMR (DMSO-d6) δ 8.34 (s, 1H, H-8), 8.15 (s, 1H, H-2), 7.48, 7.37, 7.28 (bs, NHs), 5.87 (d, 1H, H-1′, J1′,2′=5.2 Hz), 5.50 (d, 1H, 2′-OH, J2′-2′OH=5.7 Hz), 5.28 (d, 1H, 3′-OH, J3′-3′OH=4.5 Hz), 4.65 (ddd, 1H, H-2′, J1′,2′=5.2 Hz, J2′,3′=5.1 Hz, J2′-2′OH=5.7 Hz), 4.12 (ddd, 1H, H-3′, J2′,3′=5.1 Hz, J3′,4′=4.6 Hz, J3′-3′OH=4.5 Hz), 4.0-4.10 (bm, 1H, H-4′), 3.30-3.50 (bm, 2H, 5′-CH2), 3.12-3.28 (bm, 2H, NH—CH2), 2.55-2.65 (bm, 2H, N(CH3)—CH2), 2.25 (bs, 3H, N—CH3); UV λmax, nm, pH 1, 256.3 (∈ 10,900), pH 7, 259 (∈ 11,300), pH 13, 259 (∈ 11,000). Anal. (C14H23N9O3.0.05CHCl3.3.5H2O) C, H, N.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. customthe product was purified by column chromatography (silica gel 230-400 mesh, elution with 4:1:0.3 chloroform:methanol:NH4OH)
  3. concentrationconcentrated
  4. customdried in vacuo
  5. customto give a white solid

Sources & evidence

ORD record
ord-b92d22070c4346d3a9329cfaf81c8b2b
Source dataset
uspto-grants-2014_01
Patent number
US08637485B2

Reaction notes

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