1,1-Dichloroethane → 6-(difluoro(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)-3-methoxyquinoline

HRID 2176642Notes

Reaction equation

HRID 2176642 reaction equation
[F:1][C:2]([F:32])([C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[N:26]=[CH:25][C:24]([O:30][CH3:31])=[CH:23]2)[C:3]([NH:5][NH:6][C:7]1[C:12]([F:13])=[CH:11][C:10]([C:14]2[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=2)=[CH:9][N:8]=1)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.ClC(Cl)C.C(N(C(C)C)CC)(C)C.ClC(Cl)(Cl)C#N>CO>[F:1][C:2]([F:32])([C:3]1[N:8]2[CH:9]=[C:10]([C:14]3[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=3)[CH:11]=[C:12]([F:13])[C:7]2=[N:6][N:5]=1)[C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[N:26]=[CH:25][C:24]([O:30][CH3:31])=[CH:23]2

Participants

7

Reactant 5

HCID 63651,1-DichloroethaneHCID 11011TrichloroacetonitrileHCID 11776TriphenylphosphineHCID 81531DiisopropylethylamineHCID 576913272,2-difluoro-N'-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-2-(3-methoxyquinolin-6-yl)acetohydrazide

Product 1

HCID 441811496-(difluoro(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)-3-methoxyquinolineYield 44%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A sealable microwave vial was charged with 2,2-difluoro-N′-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-2-(3-methoxyquinolin-6-yl)acetohydrazide (225 mg, 509 μmol) and polymer supported triphenylphosphine (2.3 mmol/g, 221 mg, 509 μmol). The flask was sealed and dichloroethane (4 mL) was added followed by diisopropylethylamine (89 μl, 509 μmol) and 2,2,2-trichloroacetonitrile (127 μl, 1271 μmol). The resulting mixture was irradiated in a microwave (Biotage Initiator) at 150° C. for 40 min. The reaction mixture was filtered and the filter cake was washed with CH2Cl2 (15 mL) and MeOH (10 mL). The filtrate was concentrated in vacuo and the resulting crude residue was purified by MPLC using 100% CH2Cl2 to 98:2 CH2Cl2: MeOH to afford 6-(difluoro(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)-3-methoxyquinoline (94 mg, 44% yield) as a tan amorphous solid. LRMS (EST) m/z calcd for C21H16F3N6O (M+H) 425.1. found 425.4.

Workup

  1. customThe flask was sealed
  2. customThe resulting mixture was irradiated in a microwave (Biotage Initiator) at 150° C. for 40 min
  3. filtrationThe reaction mixture was filtered
  4. washthe filter cake was washed with CH2Cl2 (15 mL) and MeOH (10 mL)
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe resulting crude residue was purified by MPLC

Sources & evidence

ORD record
ord-326603f39efc4a71a984f3eed06899d4
Source dataset
uspto-grants-2015_06
Patent number
US09066954B2

Reaction notes

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