N-(2-amino-4-(tert-butyl)phenyl)-3-(3-((((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)cyclobutyl)propanamide → HCID 178491020, compound

HRID 511695Notes

Reaction equation

HRID 511695 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[NH:12][C:13](=O)[CH2:14][CH2:15][CH:16]1[CH2:19][CH:18]([N:20]([CH2:24][C@@H:25]2[C@@H:32]3[C@@H:28]([O:29][C:30]([CH3:34])([CH3:33])[O:31]3)[C@H:27]([N:35]3[C:39]4[N:40]=[CH:41][N:42]=[C:43]([NH:44][CH2:45][C:46]5[CH:51]=[CH:50][C:49]([O:52][CH3:53])=[CH:48][C:47]=5[O:54][CH3:55])[C:38]=4[CH:37]=[CH:36]3)[O:26]2)[CH:21]([CH3:23])[CH3:22])[CH2:17]1>CC(O)=O>[C:8]([C:6]1[CH:5]=[CH:4][C:3]2[NH:12][C:13]([CH2:14][CH2:15][CH:16]3[CH2:17][CH:18]([N:20]([CH2:24][C@@H:25]4[C@H:32]5[O:31][C:30]([CH3:33])([CH3:34])[O:29][C@H:28]5[C@H:27]([N:35]5[C:39]6[N:40]=[CH:41][N:42]=[C:43]([NH:44][CH2:45][C:46]7[CH:51]=[CH:50][C:49]([O:52][CH3:53])=[CH:48][C:47]=7[O:54][CH3:55])[C:38]=6[CH:37]=[CH:36]5)[O:26]4)[CH:21]([CH3:22])[CH3:23])[CH2:19]3)=[N:1][C:2]=2[CH:7]=1)([CH3:9])([CH3:11])[CH3:10]

Participants

3

Reactant 1

HCID 67775308N-(2-amino-4-(tert-butyl)phenyl)-3-(3-((((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)cyclobutyl)propanamide

Product 1

HCID 178491020HCID 178491020, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
65 °C

Procedure

N-(2-Amino-4-(tert-butyl)phenyl)-3-(3-((((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)cyclobutyl)propanamide (670 mg, 0.87 mmol) was dissolved in HOAc (8 mL) and then heated to 65° C. with stirring overnight. Solvent was removed in vacuo. The residue was dissolved in DCM (60 mL), then washed with NaHCO3 (sat. 20 mL) and water (20 mL), the organic phase was dried and concentrated. The crude was purified by Prep-TLC (DCM:MeOH=10:1) to afford the desired compound (470 mg, yield: 73%) as a white solid, which was then separated by Chiral HPLC to afford cis (243 mg) and trans isomers (180 mg) as a white solids.

Workup

  1. customSolvent was removed in vacuo
  2. dissolutionThe residue was dissolved in DCM (60 mL)
  3. washwashed with NaHCO3 (sat. 20 mL) and water (20 mL)
  4. customthe organic phase was dried
  5. concentrationconcentrated
  6. customThe crude was purified by Prep-TLC (DCM:MeOH=10:1)

Sources & evidence

ORD record
ord-bcd7108fd1154085be80eb781f996806
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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