Diisopropylethylamine → N-(2-amino-4-(tert-butyl)phenyl)-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)(isobutyl)amino)cyclobutyl)propanamide

HRID 511656Notes

Reaction equation

HRID 511656 reaction equation
[CH3:1][O:2][C:3]1[CH:44]=[C:43]([O:45][CH3:46])[CH:42]=[CH:41][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]([CH2:37][CH:38]([CH3:40])[CH3:39])[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.[C:56]([C:60]1[CH:61]=[C:62]([NH2:67])[C:63]([NH2:66])=[CH:64][CH:65]=1)([CH3:59])([CH3:58])[CH3:57]>CN(C)C=O>[NH2:67][C:62]1[CH:61]=[C:60]([C:56]([CH3:59])([CH3:57])[CH3:58])[CH:65]=[CH:64][C:63]=1[NH:66][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:41]=[CH:42][C:43]([O:45][CH3:46])=[CH:44][C:3]=5[O:2][CH3:1])[C:8]=4[CH:15]=[CH:14]3)[CH2:17]2)[CH2:37][CH:38]([CH3:39])[CH3:40])[CH2:29]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 4327084-Tert-butylbenzene-1,2-diamineHCID 677753833-(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)(isobutyl)amino)cyclobutyl)propanoic acid

Product 1

HCID 67774095N-(2-amino-4-(tert-butyl)phenyl)-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)(isobutyl)amino)cyclobutyl)propanamideYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N,N,N′,N′-Tetramethyl-0-(7-azabenzotriazol-1-yl)uronium Hexafluorophosphate (1.52 g, 4.01 mmol) added to a solution of 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)(isobutyl)amino)cyclobutyl)propanoic acid (1.7 g, 2.7 mmol) and N,N-Diisopropylethylamine (1.54 ml, 8.82 mmol) and 4-tert-butylbenzene-1,2-diamine (0.527 g, 3.21 mmol) in N,N-Dimethylformamide (16.6 ml). The reaction was stirred overnight at RT, partially concentrated to ca. 2 mls and then NaHCO3 (saturated) added. Them mixture was extracted with EtOAc 3× and the combined organics were dried with MgSO4 filtered, concentrated and purified by flash chromatography (DCM/7N NH3 in MeOH 95:5) to yield the desired amide (1.71 g) as a solid.

Workup

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

Sources & evidence

ORD record
ord-3ddabc7e772c45d9b03dbef59e8e70d9
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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