2-Methoxyethanol → 4-(Octahydro-pyrrolo[1,2-a]pyrazin-2-yl)-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-ylamine

HRID 1027889Notes

Reaction equation

HRID 1027889 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[NH:23][CH2:22][CH2:21][N:20]2[CH2:24][CH2:25][CH2:26][CH:19]12.COCCO.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[CH2:18]1[N:23]([C:2]2[C:3]3[CH2:13][CH2:12][CH2:11][C:10]4[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=4[C:4]=3[N:5]=[C:6]([NH2:8])[N:7]=2)[CH2:22][CH2:21][N:20]2[CH2:24][CH2:25][CH2:26][CH:19]12

Participants

6

Reactant 4

HCID 80192-MethoxyethanolHCID 81531DiisopropylethylamineHCID 558578Octahydropyrrolo(1,2-a)pyrazineHCID 866218984-chloro-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-amine

Product 1

HCID 250738184-(Octahydro-pyrrolo[1,2-a]pyrazin-2-yl)-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-ylamine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
115 °C

Procedure

The product from Example 68A (40 mg, 0.16 mmol) was treated with octahydro-pyrrolo[1,2-A]pyrazine (31 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 organic layers were dried (MgSO4), filtered, concentrated and purified by chromatography (eluting with 2, 3.5, 5 and 10% (9:1 MeOH:saturated aqueous NH4OH) in CH2Cl2) to provide the title compound. 1H NMR (CDCl3) δ 1.43-1.57 (m, 1H), 1.71-1.94 (m, 3H), 2.13-2.29 (m, 4H), 2.30-2.45 (m, 3H), 2.66 (t, J=6.78 Hz, 2H), 2.81 (dd, J=12.21, 10.17 Hz, 1H), 3.06-3.23 (m, 3H), 3.81-3.89 (m, 1H), 3.98 (dt, J=12.29, 2.33 Hz, 1H), 4.76 (s, 2H), 7.20-7.24 (m, 1H), 7.31-7.39 (m, 2H), 7.71-7.76 (m, 1H); MS (M+H)+ m/z 336.

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 organic layers were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by chromatography (eluting with 2, 3.5, 5 and 10% (9:1 MeOH:saturated aqueous NH4OH) in CH2Cl2)

Sources & evidence

ORD record
ord-1a7c2b89c2114fe385e887592fff6ead
Source dataset
uspto-grants-2014_05
Patent number
US08735411B2

Reaction notes

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