Diisopropylethylamine → [4-(6-Chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-cyclohexylmethyl]-carbamic Acid Tert-butyl Ester

HRID 220791Notes

Reaction equation

HRID 220791 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH:13]([C:16]([OH:18])=O)[CH2:12][CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[Cl:52][C:53]1[CH:54]=[CH:55][C:56]2[NH:65][CH2:64][C:63]3[CH:62]=[N:61][N:60]([CH3:66])[C:59]=3[NH:58][C:57]=2[CH:67]=1>ClCCl>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][CH:10]1[CH2:11][CH2:12][CH:13]([C:16]([N:65]2[CH2:64][C:63]3[CH:62]=[N:61][N:60]([CH3:66])[C:59]=3[NH:58][C:57]3[CH:67]=[C:53]([Cl:52])[CH:54]=[CH:55][C:56]2=3)=[O:18])[CH2:14][CH2:15]1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 736918(1r,4r)-4-((((Tert-butoxy)carbonyl)amino)methyl)cyclohexane-1-carboxylic acidHCID 2733179PyBroPHCID 1357360546-Chloro-3-methyl-3,4,9,10-tetrahydro-2,3,4,9-tetraaza-benzo[f]azulene

Product 1

HCID 136128395[4-(6-Chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-cyclohexylmethyl]-carbamic Acid Tert-butyl EsterYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 4-(tert-butoxycarbonylamino-methyl)-cyclohexanecarboxylic acid from Example E9 (510 mg, 2.0 mmol) in dichloromethane (25 ml) at room temperature was treated with DIEA (0.70 ml, 4.0 mmol), PyBrop (2.40 g, 5.1 mmol), and 6-chloro-3-methyl-3,4,9,10-tetrahydro-2,3,4,9-tetraaza-benzo[f]azulene from Example E1 (422 mg, 1.8 mmol) and the resulting solution was heated at reflux for 20 h and allowed to cool to room temperature. The solution was diluted with dichloromethane, washed with brine and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant EtOAc) to yield the title compound (775 mg, 91%).

Workup

  1. temperaturethe resulting solution was heated
  2. temperatureat reflux for 20 h
  3. washwashed with brine
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography on silica gel (eluant EtOAc)

Sources & evidence

ORD record
ord-bc9593b379614bab950016dac46a80db
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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