Dimethylformamide → N-(2-amino-4-(trifluoromethoxy)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)(isopropyl)amino)cyclobutyl)propanamide

HRID 511661Notes

Reaction equation

HRID 511661 reaction equation
[CH3:1][O:2][C:3]1[CH:43]=[C:42]([O:44][CH3:45])[CH:41]=[CH:40][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:37]([CH3:39])[CH3:38])[CH:28]4[CH2:31][CH:30]([CH2:32][CH2:33][C:34]([OH:36])=O)[CH2:29]4)[CH2:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1.C(N(CC)C(C)C)(C)C.[F:55][C:56]([F:67])([F:66])[O:57][C:58]1[CH:59]=[C:60]([NH2:65])[C:61]([NH2:64])=[CH:62][CH:63]=1.CN(C)C=O>>[NH2:65][C:60]1[CH:59]=[C:58]([O:57][C:56]([F:55])([F:66])[F:67])[CH:63]=[CH:62][C:61]=1[NH:64][C:34](=[O:36])[CH2:33][CH2:32][CH:30]1[CH2:29][CH:28]([N:27]([CH2:26][C@@H:18]2[C@@H:19]3[C@@H:20]([O:21][C:22]([CH3:25])([CH3:24])[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:40]=[CH:41][C:42]([O:44][CH3:45])=[CH:43][C:3]=5[O:2][CH3:1])[C:8]=4[CH:15]=[CH:14]3)[CH2:17]2)[CH:37]([CH3:39])[CH3:38])[CH2:31]1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 27739594-(Trifluoromethoxy)benzene-1,2-diamineHCID 677774723-(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)(isopropyl)amino)cyclobutyl)propanoic acid

Product 1

HCID 67774050N-(2-amino-4-(trifluoromethoxy)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)(isopropyl)amino)cyclobutyl)propanamide

Procedure

N,N,N′,N′-Tetramethyl-0-(7-azabenzotriazol-1-yl)uronium Hexafluorophosphate (1.19 g, 3.14 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)(isopropyl)amino)cyclobutyl)propanoic acid (1.3 g, 2.1 mmol) and N,N-Diisopropylethylamine (1.20 mL, 6.90 mmol) and 4-(trifluoromethoxy)benzene-1,2-diamine (0.482 g, 2.51 mmol) in N,N-Dimethylformamide (13.0 mL, 167 mmol). The reaction was stirred overnight at RT and was 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 chromatogrpahy (DCM/7N NH3 in MeOH 95:5) to the desired amide (1.4 g) as a solid.

Workup

  1. concentrationwas partially 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 chromatogrpahy (DCM/7N NH3 in MeOH 95:5) to the desired amide (1.4 g) as a solid

Sources & evidence

ORD record
ord-110b5a3ae2ad47a59bc662a33110e0ee
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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