Diisopropylethylamine → 4-{3-[2-Methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenoxy]-propyl}-piperidine-1-carboxylic Acid Tert-butyl Ester

HRID 220898Notes

Reaction equation

HRID 220898 reaction equation
C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][CH:35]([CH2:38][CH2:39][CH2:40][O:41][C:42]2[CH:47]=[CH:46][C:45]([C:48]([OH:50])=O)=[CH:44][C:43]=2[CH3:51])[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].[CH3:52][N:53]1[C:62]2[NH:61][C:60]3[CH:63]=[CH:64][CH:65]=[CH:66][C:59]=3[NH:58][CH2:57][C:56]=2[CH:55]=[N:54]1.CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.ClCCl>[C:25]([O:29][C:30]([N:32]1[CH2:33][CH2:34][CH:35]([CH2:38][CH2:39][CH2:40][O:41][C:42]2[CH:47]=[CH:46][C:45]([C:48]([N:58]3[CH2:57][C:56]4[CH:55]=[N:54][N:53]([CH3:52])[C:62]=4[NH:61][C:60]4[CH:63]=[CH:64][CH:65]=[CH:66][C:59]3=4)=[O:50])=[CH:44][C:43]=2[CH3:51])[CH2:36][CH2:37]1)=[O:31])([CH3:27])([CH3:26])[CH3:28]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 57555240HCID 57555240, compoundHCID 1357419771-Methyl-1,4,5,10-tetrahydrobenzo[b]pyrazolo[3,4-e][1,4]diazepine

Product 1

HCID 1361284404-{3-[2-Methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-phenoxy]-propyl}-piperidine-1-carboxylic Acid Tert-butyl EsterYield 40%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

PyBroP (224 mg, 0.48 mmol) and DMAP (39 mg, 0.32 mmol) were added to a solution of 4-[3-(4-carboxy-2-methyl-phenoxy)-propyl]-piperidine-1-carboxylic acid tert-butyl ester from Example E68.3 (120 mg, 0.32 mmol) and 3-methyl-3,4,9,10-tetrahydro-2,3,4,9-tetraaza-benzo[f]azulene from Example E11 (70 mg, 0.35 mmol) in dichloromethane (5 ml) and DIEA (0.111 ml, 0.64 mmol). The mixture was heated at reflux for 2 days, washed with saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloro-methane) to yield the title compound (71 mg, 40%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 2 days
  3. washwashed with saturated NaHCO3
  4. dry with materialbrine, dried
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloro-methane)

Sources & evidence

ORD record
ord-e4edf03118314826967cf95dfbf19a31
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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