Isopropanol → HCID 68680102, compound

HRID 1174620Notes

Reaction equation

HRID 1174620 reaction equation
Cl[C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[C:4]([C@H](C)COC)[N:3]=1.[CH:16]1([NH:19][C:20]([C:22]2[CH:23]=[C:24]([F:32])[C:25]([CH3:31])=[C:26](B(O)O)[CH:27]=2)=[O:21])[CH2:18][CH2:17]1.[C:33](=[O:36])([O-])O.[Na+].[CH3:38][CH:39](O)[CH3:40]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:16]1([NH:19][C:20]([C:22]2[CH:23]=[C:24]([F:32])[C:25]([CH3:31])=[C:26]([C:2]3[N:3]=[CH:4][C:5]([C:6]([NH:8][C@@H:39]([CH3:40])[CH2:38][O:36][CH3:33])=[O:7])=[CH:9][CH:10]=3)[CH:27]=2)=[O:21])[CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 516892Sodium BicarbonateHCID 21914527(5-(Cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl)boronic acid2×HCID 86613567HCID 86613567, compound2×

Product 1

HCID 68680102HCID 68680102, compound

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

6-Chloro-[(S)-1-methoxy-2-propyl]nicotinamide (Intermediate 14, 100 mg), {5-[(cyclopropylamino)carbonyl]-3-fluoro-2-methylphenyl}boronic acid (Intermediate 6, 100 mg), tetrakis(triphenylphosphine)palladium (10 mg) and aqueous sodium hydrogen carbonate (4 ml) were mixed in propan-2-ol (8 ml) and heated at 90° C. under nitrogen for 18 hrs. The solvents were evaporated from the cooled reaction under vacuum and the residue dissolved as far as possible in ethylacetate. The solution was applied to an SPE (SCX, 10 g) and washed with ethyl acetate. The product was eluted from the column with methanol/0.880 ammonia, and the solvents evaporated in vacuo. The residue was redissolved in ethyl acetate and filtered through an SPE (silica, 0.5 g). The filtrate was reduced to dryness under vacuum and triturated with ether to give 6-{5-[(cyclopropylamino)carbonyl]-3-fluoro-2-methylphenyl}-N-[(1S)-1-methyl-2-(methyloxy)ethyl]-3-pyridinecarboxamide.

Workup

  1. customThe solvents were evaporated from the cooled reaction under vacuum
  2. dissolutionthe residue dissolved as far as possible in ethylacetate
  3. washwashed with ethyl acetate
  4. washThe product was eluted from the column with methanol/0.880 ammonia
  5. customthe solvents evaporated in vacuo
  6. dissolutionThe residue was redissolved in ethyl acetate
  7. filtrationfiltered through an SPE (silica, 0.5 g)
  8. customtriturated with ether

Sources & evidence

ORD record
ord-a0b6ee57d3b74717aff47d8ea5221331
Source dataset
uspto-grants-2010_11
Patent number
US07838540B2

Reaction notes

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