2-Methoxyethanol → tert-Butyl 2-(2-amino-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl)octahydro-5H-pyrrolo[3,4-c]pyridine-5-carboxylate

HRID 1027888Notes

Reaction equation

HRID 1027888 reaction equation
Cl[C:2]1[C:3]2[CH2:13][CH2:12][CH2:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[C:4]=2[N:5]=[C:6]([NH2:8])[N:7]=1.[CH2:18]1[CH:26]2[CH:21]([CH2:22][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:24][CH2:25]2)[CH2:20][NH:19]1.COCCO.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[NH2:8][C:6]1[N:7]=[C:2]([N:19]2[CH2:18][CH:26]3[CH:21]([CH2:22][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:24][CH2:25]3)[CH2:20]2)[C:3]2[CH2:13][CH2:12][CH2:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[C:4]=2[N:5]=1

Participants

6

Reactant 4

HCID 80192-MethoxyethanolHCID 81531DiisopropylethylamineHCID 19691292tert-Butyl octahydro-5H-pyrrolo(3,4-c)pyridine-5-carboxylateHCID 866218984-chloro-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-amine

Product 1

HCID 86621897tert-Butyl 2-(2-amino-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-4-yl)octahydro-5H-pyrrolo[3,4-c]pyridine-5-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
115 °C

Procedure

The product from Example 68A (40 mg, 0.16 mmol) was mixed with tert-butyl hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate (55 mg, 0.24 mmol) and to this was added 2-methoxyethanol (0.65 mL), and N,N-diisopropylethylamine (0.20 mL, 1.2 mmol); the reaction was heated at 115° C. for 16 hours, cooled, diluted with CH2Cl2 (25 mL) and washed with 1 M NaOH (10 mL). The aqueous layer was extracted with CH2Cl2 (15 mL). The combined organics were dried (MgSO4), filtered, concentrated and chromatographed and eluted with a gradient of 1:0 to 0:1 CH2Cl2:EtOAc to provide the title compound.

Workup

  1. temperaturecooled
  2. washwashed with 1 M NaOH (10 mL)
  3. extractionThe aqueous layer was extracted with CH2Cl2 (15 mL)
  4. dry with materialThe combined organics were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customchromatographed
  8. washeluted with a gradient of 1:0 to 0:1 CH2Cl2

Sources & evidence

ORD record
ord-2a8c6eb47bfd4b0687dbd936dc4b2484
Source dataset
uspto-grants-2014_05
Patent number
US08735411B2

Reaction notes

Loading…