N-methyl-2-pyrrolidone → HCID 71626821, compound

HRID 1396342Notes

Reaction equation

HRID 1396342 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]([NH2:10])=[O:9])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][N:13]=2)[CH:3]=1.[C@@H:22]1([NH2:29])[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]1[NH2:28].CN1CCCC1=O>CO>[NH2:28][C@H:23]1[CH2:24][CH2:25][CH2:26][CH2:27][C@H:22]1[NH:29][C:2]1[N:7]=[N:6][C:5]([C:8]([NH2:10])=[O:9])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][N:13]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 3429171,2-Diaminocyclohexane, cis-HCID 86689712HCID 86689712, compound

Product 1

HCID 71626821HCID 71626821, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 6-chloro-4-(5-(methylsulfonyl)pyridin-2-ylamino)pyridazine-3-carboxamide (60 mg, 0.183 mmol), cis-cyclohexane-1,2-diamine (125 mg, 1.1 mmol) and N-methyl-2-pyrrolidinone (2 mL) was heated to 150° C. After 18 h, the reaction mixture was cooled and concentrated in vacuo. Purification by chromatography (spherical silica 20-45 uM, 23 g, Versaflash Supelco, 0 to 5% MeOH containing 10% NH4OH in CH2Cl2, 20 min) gave a solid residue. This residue was dissolved in MeOH and CH2Cl2, then precipitated by addition of cyclohexane. The solid formed was obtained by decantation of the mother liquor, then dried to give 6-(cis-2-aminocyclohexylamino)-4-(5-(methylsulfonyl)pyridin-2-ylamino)pyridazine-3-carboxamide (19 mg, 45.6 μmol, 25%) as a beige solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 12.21 (s, 1H) 8.73 (d, J=2.27 Hz, 1H) 8.48 (br. s., 1H) 8.16 (s, 1H) 8.12 (dd, J=8.69, 2.64 Hz, 1H) 7.75 (br. s., 1H) 7.14 (d, J=8.69 Hz, 1H) 7.03 (d, J=7.93 Hz, 1H) 4.06 (br. s., 1H) 3.26 (s, 3H) 3.09 (br. s., 1H) 1.24-1.78 (m, 10H). LCMS (EI/CI) m/z: 406 [M+H].

Workup

  1. temperaturethe reaction mixture was cooled
  2. concentrationconcentrated in vacuo
  3. customPurification by chromatography (spherical silica 20-45 uM, 23 g, Versaflash Supelco, 0 to 5% MeOH containing 10% NH4OH in CH2Cl2, 20 min)
  4. customgave a solid residue
  5. customCH2Cl2, then precipitated by addition of cyclohexane
  6. customThe solid formed
  7. customwas obtained by decantation of the mother liquor
  8. customdried

Sources & evidence

ORD record
ord-bcf39ef8496b4165a531b734daa5798d
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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