Methanol → 1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-n-(2'-hydroxy-4,5'-dimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamide

HRID 869954Notes

Reaction equation

HRID 869954 reaction equation
[F:1][C:2]1([F:33])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[C:24]([O:30]C)=[N:25][CH:26]=[C:27]([CH3:29])[CH:28]=5)[CH:20]=[C:19]([CH3:32])[CH:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.[Si](I)(C)(C)C.CO>CC#N>[F:33][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[C:24]([OH:30])=[N:25][CH:26]=[C:27]([CH3:29])[CH:28]=5)[CH:20]=[C:19]([CH3:32])[CH:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1

Participants

5

Reactant 3

HCID 887MethanolHCID 85247Trimethylsilyl iodideHCID 68737513HCID 68737513, compound

Product 1

HCID 1784286081-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-n-(2'-hydroxy-4,5'-dimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamideYield 94.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(2′-methoxy-4,5′-dimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (70 mg, 0.15 mmol) in CH3CN (3 mL) was added TMSI (44 uL, 0.30 mmol) dropwise at 20° C. The reaction was stirred at 50° C. for 30 min. MeOH (1.0 mL) was added and the solution was re-partitioned between EtOAc and H2O, washed with NaHSO3 (2×), brine, dried over MgSO4 and evaporated to dryness to yield a white solid. The crude material was further purified by column chromatography (0-10% MeOH-EtOAc) to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(2′-hydroxy-4,5′-dimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (62 mg, 91%). H NMR (400 MHz, MeOD) 7.81 (s, 2H), 7.65 (s, 1H), 7.31 (d, J=1.5 Hz, 1H), 7.25 (dd, J=1.7, 8.3 Hz, 1H), 7.17-7.14 (m, 2H), 2.29 (s, 3H), 2.03 (s, 3H), 1.57 (dd, J=4.0, 7.0 Hz, 2H), 1.15 (dd, J=4.0, 7.0 Hz, 2H). Retention time: 1.42 min; ESI-MS m/z calc. 439.4. found 440.5 (M+H)+.

Workup

  1. customthe solution was re-partitioned between EtOAc and H2O
  2. washwashed with NaHSO3 (2×), brine
  3. dry with materialdried over MgSO4
  4. customevaporated to dryness
  5. customto yield a white solid
  6. customThe crude material was further purified by column chromatography (0-10% MeOH-EtOAc)

Sources & evidence

ORD record
ord-574826557eeb47dab39e0eb64e61cefa
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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