N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxamide → HCID 68740579, compound

HRID 869928Notes

Reaction equation

HRID 869928 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[CH:9]=[CH:8][C:7](B2OC(C)(C)C(C)(C)O2)=[CH:6][C:5]1=[O:19].Cl[C:21]1[N:26]=[C:25]([NH:27][C:28]([C:30]2([C:33]3[CH:43]=[CH:42][C:36]4[O:37][C:38]([F:41])([F:40])[O:39][C:35]=4[CH:34]=3)[CH2:32][CH2:31]2)=[O:29])[CH:24]=[CH:23][C:22]=1[CH3:44]>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.C([O-])([O-])=O.[Na+].[Na+]>[F:41][C:38]1([F:40])[O:37][C:36]2[CH:42]=[CH:43][C:33]([C:30]3([C:28]([NH:27][C:25]4[CH:24]=[CH:23][C:22]([CH3:44])=[C:21]([C:7]5[CH:8]=[CH:9][N:4]([CH2:3][CH2:2][OH:1])[C:5](=[O:19])[CH:6]=5)[N:26]=4)=[O:29])[CH2:32][CH2:31]3)=[CH:34][C:35]=2[O:39]1

Participants

5

Reactant 2

HCID 59165796N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxamideHCID 687373911-(2-Hydroxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2(1H)-pyridinone

Product 1

HCID 68740579HCID 68740579, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
120 °C

Procedure

1-(2-Hydroxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (0.14 mmol) was added to a microwave vial containing N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (51 mg, 0.14 mmol) and Pd(PPh3)4 (8.0 mg, 0.0070 mmol). Saturated aqueous Na2CO3 (70 μL) was added and the reaction vial was flushed with N2 (g) and sealed. The reaction was heated in the microwave at 120° C. for 20 minutes before being filtered and concentrated. The residue was dissolved in DMSO and purified by reverse-phase HPLC to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6-(1-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridin-4-yl)-5-methylpyridin-2-yl)cyclopropanecarboxamide. ESI-MS m/z calc. 469.1. found 470.5 (M+1)+. Retention time 1.58 minutes. 1H NMR (400 MHz, DMSO-d6) δ 8.87 (s, 1H), 7.91 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.5 Hz, 1H), 7.63 (d, J=6.9 Hz, 1H), 7.56 (d, J=1.6 Hz, 1H), 7.41 (d, J=8.3 Hz, 1H), 7.34 (dd, J=1.7, 8.3 Hz, 1H), 6.39 (d, J=1.8 Hz, 1H), 6.26 (dd, J=1.9, 6.9 Hz, 1H), 3.96 (t, J=5.4 Hz, 2H), 3.63 (t, J=5.5 Hz, 2H), 2.26 (s, 3H), 1.52-1.50 (m, 2H), 1.19-1.16 (m, 2H).

Workup

  1. customthe reaction
  2. customvial was flushed with N2 (g)
  3. customsealed
  4. filtrationbefore being filtered
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in DMSO
  7. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-5d97dee6873a40ebafe7e1ece0068916
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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