Diisopropylethylamine → 4-[5-{[2-Fluoro-6-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]-6-methoxy-N,N-dimethylpyrimidin-2-amine

HRID 1524949Notes

Reaction equation

HRID 1524949 reaction equation
[CH2:1]1[CH:5]2[CH2:6][NH:7][CH2:8][CH:4]2[CH2:3][N:2]1[C:9]1[CH:14]=[C:13]([O:15][CH3:16])[N:12]=[C:11]([N:17]([CH3:19])[CH3:18])[N:10]=1.[F:20][C:21]1[CH:29]=[CH:28][CH:27]=[C:26]([N:30]2[N:34]=[CH:33][CH:32]=[N:31]2)[C:22]=1[C:23](O)=[O:24].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(OCC)(=O)C.CN(C=O)C>[F:20][C:21]1[CH:29]=[CH:28][CH:27]=[C:26]([N:30]2[N:34]=[CH:33][CH:32]=[N:31]2)[C:22]=1[C:23]([N:7]1[CH2:6][CH:5]2[CH2:1][N:2]([C:9]3[CH:14]=[C:13]([O:15][CH3:16])[N:12]=[C:11]([N:17]([CH3:18])[CH3:19])[N:10]=3)[CH2:3][CH:4]2[CH2:8]1)=[O:24]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 670866272-Fluoro-6-(2H-1,2,3-triazol-2-yl)benzoic acidHCID 67116268[4-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-6-methoxy-pyrimidin-2-yl]-dimethyl-amine

Product 1

HCID 529178124-[5-{[2-Fluoro-6-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]-6-methoxy-N,N-dimethylpyrimidin-2-amineYield 81.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of [4-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-6-methoxy-pyrimidin-2-yl]-dimethyl-amine (60.0 mg, 0.23 mmol), 2-fluoro-6-[1,2,3]triazol-2-yl-benzoic acid (52.0 mg, 0.25 mmol), HATU (130.0 mg, 0.34 mmol) and DIPEA (0.12 mL, 0.68 mmol) was stirred into DMF (4.0 mL) at room temperature for 30 minutes. The reaction mixture was diluted with ethyl acetate (60.0 mL) and washed with water (2×100 mL). The organic phase was dried (Na2SO4), filtered and concentrated to dryness to yield crude title compound (354.0 mg, 343%). The crude product was purified using Agilent HPLC (Basic system) to yield pure title compound (84.0 mg, 81.5%). MS (ESI) mass calcd. for C22H25FN8O2,452.49; m/z found 453.3 [M+H]+. 1H NMR (CDCl3): 7.88-7.79 (m, 2H), 7.72 (d, J=6.7, 1H), 7.54-7.41 (m, 1H), 7.19-7.08 (m, 1H), 5.02-4.92 (m, 1H), 3.96-3.86 (m, 1H), 3.87-3.83 (m, 3H), 3.81-3.50 (m, 5H), 3.43-3.19 (m, 2H), 3.15-3.09 (m, 6H)), 3.09-2.91 (m, 2H).

Workup

  1. washwashed with water (2×100 mL)
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. customto yield crude title compound (354.0 mg, 343%)
  6. customThe crude product was purified

Sources & evidence

ORD record
ord-4e28aaf3c07c4f0cab464263f4aee72e
Source dataset
uspto-grants-2015_07
Patent number
US09079911B2

Reaction notes

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