Water → 6-[(S)-4-(4-Chloro-6,7-dihydro-5H-cyclopenta[d]pyridazin-1-yl)-3-methyl-piperazin-1-yl]-nicotinic acid methyl ester

HRID 1479995Notes

Reaction equation

HRID 1479995 reaction equation
Cl[C:2]1[C:7]2[CH2:8][CH2:9][CH2:10][C:6]=2[C:5]([Cl:11])=[N:4][N:3]=1.[CH2:12]([O:14][C:15]([C:17]1N=[CH:19][C:20]([N:23]2[CH2:28][CH2:27][NH:26][C@@H:25]([CH3:29])[CH2:24]2)=[N:21][CH:22]=1)=[O:16])C.[CH2:30](N(CC)CC)C.O>CN1C(=O)CCC1.CCOC(C)=O>[CH3:12][O:14][C:15](=[O:16])[C:17]1[CH:30]=[CH:19][C:20]([N:23]2[CH2:28][CH2:27][N:26]([C:2]3[C:7]4[CH2:8][CH2:9][CH2:10][C:6]=4[C:5]([Cl:11])=[N:4][N:3]=3)[C@@H:25]([CH3:29])[CH2:24]2)=[N:21][CH:22]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 154019081,4-dichloro-5H,6H,7H-cyclopenta[d]pyridazineHCID 67177692(S)-3-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-carboxylic acid ethyl ester

Product 1

HCID 591916516-[(S)-4-(4-Chloro-6,7-dihydro-5H-cyclopenta[d]pyridazin-1-yl)-3-methyl-piperazin-1-yl]-nicotinic acid methyl esterYield 16.3%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
195 °C

Procedure

To a solution of 1,4-dichloro-6,7-dihydro-5H-cyclopenta[d]pyridazine (150 mg, 0.79 mmol) in NMP (5 mL) is added (S)-3-methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-5′-carboxylic acid ethyl ester (297 mg, 1.19 mmol) and triethyl amine (332 μL, 2.39 mmol). The reaction mixture is heated in a microwave reactor at 195° C. for 4 h. Water and EtOAc is added. The layers are separated and the aqueous layer is extracted with EtOAc. The combined organic layers are washed with water, brine, dried over Na2SO4, filtered and concentrated. The crude product is purified by flash chromatography (EtOAx/heptane 10% to 70%) to yield 50 mg (16%) of the title compound.

Workup

  1. customThe layers are separated
  2. extractionthe aqueous layer is extracted with EtOAc
  3. washThe combined organic layers are washed with water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is purified by flash chromatography (EtOAx/heptane 10% to 70%)

Sources & evidence

ORD record
ord-ea35b13a5c9340abb73a0658e9f4e65f
Source dataset
uspto-grants-2016_08
Patent number
US09409871B2

Reaction notes

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