Methanol → HCID 178430688, compound

HRID 869956Notes

Reaction equation

HRID 869956 reaction equation
[F:1][C:2]1([F:34])[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)[C:20]([CH3:32])=[C:19]([CH3:33])[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:34][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)[C:20]([CH3:32])=[C:19]([CH3:33])[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 687393981-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-n-(2'-methoxy-3,4,5'-trimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamide

Product 1

HCID 178430688HCID 178430688, compoundYield 92.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(2′-methoxy-3,4,5′-trimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (75 mg, 0.16 mmol) in CH3CN (3 mL) was added TMSI (46 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-3,4,5′-trimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (67 mg, 92%). 1H NMR (400 MHz, MeOD) 7.89 (s, 1H), 7.31-7.27 (m, 2H), 7.23-7.19 (m, 2H), 7.12 (d, J=8.3 Hz, 1H), 2.25 (s, 3H), 2.03 (s, 3H), 1.97 (s, 3H), 1.56 (dd, J=3.9, 7.0 Hz, 2H), 1.13 (dd, J=3.8, 6.9 Hz, 2H). Retention time: 1.52 min; ESI-MS m/z calc. 453.4. found 454.5 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-543b5885e5334fa8a04c1285e46d2270
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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