1,2-Dichloroethane → ethyl 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)amino)cyclobutyl)propanoate

HRID 511579

Reaction equation

HRID 511579 reaction equation
[NH2:1][CH2:2][C@@H:3]1[C@H:7]2[O:8][C:9]([CH3:12])([CH3:11])[O:10][C@H:6]2[C@H:5]([N:13]2[C:17]3[N:18]=[CH:19][N:20]=[C:21]([NH:22][CH2:23][C:24]4[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:25]=4[O:32][CH3:33])[C:16]=3[CH:15]=[CH:14]2)[CH2:4]1.ClCCCl.O=[C:39]1[CH2:42][CH:41]([CH2:43][CH2:44][C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:40]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:33][O:32][C:25]1[CH:26]=[C:27]([O:30][CH3:31])[CH:28]=[CH:29][C:24]=1[CH2:23][NH:22][C:21]1[C:16]2[CH:15]=[CH:14][N:13]([C@H:5]3[C@@H:6]4[O:10][C:9]([CH3:12])([CH3:11])[O:8][C@@H:7]4[C@@H:3]([CH2:2][NH:1][CH:39]4[CH2:40][CH:41]([CH2:43][CH2:44][C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:42]4)[CH2:4]3)[C:17]=2[N:18]=[CH:19][N:20]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 677749937-((3aS,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-N-(2,4-dimethoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amineHCID 67775333Ethyl 3-(3-oxocyclobutyl)propanoate

Product 1

HCID 67776915ethyl 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)amino)cyclobutyl)propanoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 7-((3aS,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-N-(2,4-dimethoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (8.00 g, 15.2 mmol) in 1,2-Dichloroethane (119.5 mL, 1517 mmol) was treated with ethyl 3-(3-oxocyclobutyl)propanoate (2.58 g, 15.2 mmol) and Acetic acid (0.86 mL, 15 mmol) dropwise followed by Sodium triacetoxyborohydride (3.86 g, 18.2 mmol) and the mixture was stirred at RT for 19 h. The reaction mixture was diluted with 150 mL CH2Cl2 and washed with 150 mL sat NaHCO3. The aqueous phase was washed with 70 mL CH2Cl2 and the combined organic phase was dried over Na2SO4, filtered and concentrated to yield a tan glass that produced a sticky foam when placed under high vac. The crude material was purified by flash chromatography (SiO2 eluting with 3-4% 7N NH3 in CH3OH/CH2Cl2) to yield a light yellow viscous oil that producted a sticky foam under high vacuum (5.03 g). MS 608.3 (M+H).

Workup

  1. washwashed with 150 mL
  2. washThe aqueous phase was washed with 70 mL CH2Cl2
  3. dry with materialthe combined organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto yield a tan glass that
  7. customproduced a sticky foam when
  8. customThe crude material was purified by flash chromatography (SiO2 eluting with 3-4% 7N NH3 in CH3OH/CH2Cl2)
  9. customto yield a light yellow viscous oil that

Sources & evidence

ORD record
ord-f5717ee528334b719358810cf12d586e
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Linked notes

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