Diisopropylethylamine → N-(2-amino-4-bromophenyl)-3-(3-((((3aR,4R,6R,6aS)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)propanamide

HRID 2040682Notes

Reaction equation

HRID 2040682 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]([CH3:37])[CH:28]4[CH2:31][CH:30]([CH2:32][CH2:33][C:34](O)=[O:35])[CH2:29]4)[CH2:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1.C(N(CC)C(C)C)(C)C.[Br:53][C:54]1[CH:55]=[C:56]([NH2:61])[C:57]([NH2:60])=[CH:58][CH:59]=1>CN(C)C=O>[NH2:61][C:56]1[CH:55]=[C:54]([Br:53])[CH:59]=[CH:58][C:57]=1[NH:60][C:34](=[O:35])[CH2:33][CH2:32][CH:30]1[CH2:31][CH:28]([N:27]([CH2:26][C@@H:18]2[C@@H:19]3[C@@H:20]([O:21][C:22]([CH3:24])([CH3:25])[O:23]3)[C@H:16]([N:13]3[C:9]4[N:10]=[CH:11][N:12]=[C:7]([NH:6][CH2:5][C:4]5[CH:38]=[CH:39][C:40]([O:42][CH3:43])=[CH:41][C:3]=5[O:2][CH3:1])[C:8]=4[CH:15]=[CH:14]3)[CH2:17]2)[CH3:37])[CH2:29]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 3235934-Bromobenzene-1,2-diamineHCID 677753043-(3-((((3aR,4R,6R,6aS)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)propanoic acid

Product 1

HCID 67776470N-(2-amino-4-bromophenyl)-3-(3-((((3aR,4R,6R,6aS)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)propanamideYield 74.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N,N,N′,N′-Tetramethyl-0-(7-azabenzotriazol-1-yl)uronium Hexafluorophosphate (1.20 g, 3.16 mmol) was added to a solution 3-(3-((((3aR,4R,6R,6aS)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)propanoic acid (1.25 g, 2.10 mmol) and N,N-Diisopropylethylamine (1.21 ml, 6.95 mmol) and 4-bromobenzene-1,2-diamine (0.472 g, 2.53 mmol) in N,N-Dimethylformamide (13.0 ml). The reaction was stirred overnight at RT, partially concentrated to ca. 2 mls and then NaHCO3 (saturated) was added. The mixture was extracted with EtOAc (3×) and the combined organics were dried with MgSO4, filtered and concentrated. The residue was purified by flash chromatography (DCM/7N NH3 in MeOH 95:5) to give the desired compound (1.2 g) as a solid.

Workup

  1. concentrationpartially concentrated to ca. 2 mls
  2. additionNaHCO3 (saturated) was added
  3. extractionThe mixture was extracted with EtOAc (3×)
  4. dry with materialthe combined organics were dried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (DCM/7N NH3 in MeOH 95:5)

Sources & evidence

ORD record
ord-0a03e279d43f4e71a821509873a19198
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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