Hydrazine hydrate (1:1) → HCID 178507122, compound

HRID 1509104Notes

Reaction equation

HRID 1509104 reaction equation
C(OC(=O)[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:23]=[C:22]4[CH2:24][CH2:25][CH2:26][C:27](=[CH:30]N(C)C)[C:28](=O)[C:21]4=[CH:20][C:19]=3[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)(C)(C)C.O.[NH2:42][NH2:43]>C(O)C>[C:34]1([C:19]2[CH:20]=[C:21]3[C:28]4=[N:42][NH:43][CH:30]=[C:27]4[CH2:26][CH2:25][CH2:24][C:22]3=[N:23][C:18]=2[C:15]2[CH:14]=[CH:13][C:12]([C:8]3([NH2:7])[CH2:11][CH2:10][CH2:9]3)=[CH:17][CH:16]=2)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 123722685HCID 123722685, compound

Product 1

HCID 178507122HCID 178507122, compoundYield 72.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of tert-butyl(1-(4-(6-((dimethylamino)methylene)-5-oxo-3-phenyl-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-2-yl)phenyl)cyclobutyl)carbamate (90 mg, 0.17 mmol) in anhydrous ethanol (2 mL) was added hydrazine hydrate (25 μL, 0.5 mmol). The reaction mixture was stirred at room temperature under a nitrogen atmosphere for 18 hours. The reaction mixture was concentrated to dryness under reduced pressure, purified by Biotage chromatography (silica, hexane:ethyl acetate, gradient elution from 99:1 to 60:40) and preparative HPLC (Method G, gradient 5 to 95% 0.1% FA/ACN in 0.1% FA/H2O, 20 minutes run) to give the desired product as a white solid (50 mg, 58% yield). 1H NMR (500 MHz, CDCl3) 7.49 (s, 1H), 7.38 (d, 2H), 7.29 (d, 2H), 7.21-7.25 (br m, 5H+1H), 3.25 (m, 2H), 2.94 (t, 2H), 2.53-2.61 (br m, 1H), 2.42-2.52 (m, 2H), 2.31-2.41 (br m, 1H), 2.14-2.21 (m, 2H), 1.98-2.10 (m, 1H), 1.74-1.85 (m, 1H), 1.30-1.43 (br s, 9H). LCMS (Method A): RT=6.09 min, M+H+=507.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
  2. custompurified by Biotage chromatography (silica, hexane:ethyl acetate, gradient elution from 99:1 to 60:40) and preparative HPLC (Method G, gradient 5 to 95% 0.1% FA/ACN in 0.1% FA/H2O, 20 minutes run)

Sources & evidence

ORD record
ord-fa4e065b17a144c98ae2a65bf999c025
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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