Dimethylcarbamoyl Chloride → HCID 91826342, compound

HRID 874001Notes

Reaction equation

HRID 874001 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:15]3[C:14]([CH3:16])=[N:13][NH:12][C:11]=3[C:10](=[O:17])[N:9]2[C:18]2[CH:23]=[C:22]([CH3:24])[C:21](=[O:25])[N:20]([CH3:26])[CH:19]=2)=[CH:4][CH:3]=1.[CH3:27][N:28]([CH3:32])[C:29](Cl)=[O:30]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:15]3[C:14]([CH3:16])=[N:13][N:12]([C:29]([N:28]([CH3:32])[CH3:27])=[O:30])[C:11]=3[C:10](=[O:17])[N:9]2[C:18]2[CH:23]=[C:22]([CH3:24])[C:21](=[O:25])[N:20]([CH3:26])[CH:19]=2)=[CH:4][CH:3]=1.[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:15]3[C:11](=[N:12][N:13]([C:29]([N:28]([CH3:32])[CH3:27])=[O:30])[C:14]=3[CH3:16])[C:10](=[O:17])[N:9]2[C:18]2[CH:23]=[C:22]([CH3:24])[C:21](=[O:25])[N:20]([CH3:26])[CH:19]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 6598Dimethylcarbamoyl ChlorideHCID 178434165HCID 178434165, compound

Product 2

HCID 91826342HCID 91826342, compoundHCID 91826343HCID 91826343, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A mixture of 4-(4-chlorophenyl)-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (Example 27) (200 mg, 0.542 mmol) and dimethylcarbamic chloride (0.06 mL, 0.651 mmol) in pyridine (2 mL) for 8 h at 100° C. The reaction mixture was concentrated, diluted in CH2Cl2/water, and extracted twice with CH2Cl2. The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated. The residue was purified by chromatography (1% ammonia/5% MeOH/CH2Cl2), subsequent preparative achiral SFC (column: Reprosil 70 NH2, 250×30 mm, 5 μm, Dr Maisch; eluent: MeOH/scCO2; gradient: 1 min 15% MeOH, 15-20% MeOH in 6 min, 20-50% MeOH in 1 min, 1.5 min 50% MeOH; flow: 100 mL/min) and trituration of the resulting products in diethyl ether to afford 68 mg of 4-(4-chlorophenyl)-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-N,N,3-trimethyl-6-oxo-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxamide (Example 142) and 62 mg of the title compound. tR: 0.85 min (LC-MS 2); ESI-MS: 440.1 [M+H]+ (LC-MS 2); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.95 (s, 3H) 2.15 (s, 3H) 2.95 (s, 3H) 3.08 (s, 3H) 3.38 (s, 3H) 6.22 (s, 1H) 7.33 (d, J=8.42 Hz, 2H) 7.37-7.48 (m, 3H) 7.79 (d, J=2.64 Hz, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted in CH2Cl2/water
  3. extractionextracted twice with CH2Cl2
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (1% ammonia/5% MeOH/CH2Cl2), subsequent preparative achiral SFC (column: Reprosil 70 NH2, 250×30 mm, 5 μm, Dr Maisch; eluent: MeOH/scCO2; gradient: 1 min 15% MeOH, 15-20% MeOH in 6 min, 20-50% MeOH in 1 min, 1.5 min 50% MeOH; flow: 100 mL/min) and trituration of the resulting products in diethyl ether

Sources & evidence

ORD record
ord-3ba0f6570a714972865f2e72156be26e
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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