Diisopropylethylamine → HCID 67818475, compound

HRID 1024668Notes

Reaction equation

HRID 1024668 reaction equation
[CH3:1][O:2][C:3]1[CH:41]=[C:40]([O:42][CH3:43])[CH:39]=[CH:38][C:4]=1[CH2:5][NH:6][C:7]1[C:8]2[CH:15]=[CH:14][N:13]([C@H:16]3[C@@H:20]4[O:21][C:22]([CH3:25])([CH3:24])[O:23][C@@H:19]4[C@@H:18]([CH2:26][N:27]([CH:35]([CH3:37])[CH3:36])[CH2:28][CH2:29][CH2:30][CH2:31][C:32](O)=[O:33])[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1.[C:44]([C:48]1[CH:49]=[C:50]([NH2:55])[C:51]([NH2:54])=[CH:52][CH:53]=1)([CH3:47])([CH3:46])[CH3:45].C(N(CC)C(C)C)(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C)C=O>[NH3:6].[NH2:55][C:50]1[CH:49]=[C:48]([C:44]([CH3:47])([CH3:45])[CH3:46])[CH:53]=[CH:52][C:51]=1[NH:54][C:32](=[O:33])[CH2:31][CH2:30][CH2:29][CH2:28][N:27]([CH2:26][C@@H:18]1[C@@H:19]2[C@@H:20]([O:21][C:22]([CH3:24])([CH3:25])[O:23]2)[C@H:16]([N:13]2[C:9]3[N:10]=[CH:11][N:12]=[C:7]([NH:6][CH2:5][C:4]4[CH:38]=[CH:39][C:40]([O:42][CH3:43])=[CH:41][C:3]=4[O:2][CH3:1])[C:8]=3[CH:15]=[CH:14]2)[O:17]1)[CH:35]([CH3:36])[CH3:37]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 4327084-Tert-butylbenzene-1,2-diamineHCID 2724699PyBOPHCID 678172005-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(isopropyl)amino)pentanoic acid

Product 2

HCID 222AmmoniaYield 2%HCID 67818475HCID 67818475, compoundYield 171.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(isopropyl)amino)pentanoic acid (131 mg, 0.219 mmol) and 4-tert-butylbenzene-1,2-diamine (40 mg, 0.24 mmol) in N,N-dimethylformamide (2.2 mL) was treated with N,N-diisopropylethylamine (84 uL, 0.48 mmol) dropwise followed by PyBop reagent (120 mg, 0.24 mmol). The solution was allowed to stir at room temperature for 19 h, whereupon HPLC indicated the reaction was complete. The reaction mixture was concentrated under high vacuum. The residue was taken up in 40 mL CH2Cl2 and washed with 20 mL portions of H2O, 5% citric acid, and brine. The organic phase was dried over Na2SO4, filtered and concentrated to yield a tan viscous glass. The crude material was purified by flash chromatography (40 g silica gel; 2% 7N NH3 in CH3OH/CH2Cl2 to yield the title compound (140 mg, 86%) was a slightly tan glass: MS (ESI+) for C41H57N7O6 m/z 744.9 (M+H)+; HPLC purity (combined for the two regioisomers) 91% (ret. times, 3.25 and 3.28 min).

Workup

  1. concentrationThe reaction mixture was concentrated under high vacuum
  2. washwashed with 20 mL portions of H2O, 5% citric acid, and brine
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto yield a tan viscous glass
  7. customThe crude material was purified by flash chromatography (40 g silica gel

Sources & evidence

ORD record
ord-1c9c99e98d184590b4d9529708ef7544
Source dataset
uspto-grants-2014_05
Patent number
US08722877B2

Reaction notes

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