Water → HCID 89907993, compound

HRID 525748Notes

Reaction equation

HRID 525748 reaction equation
[Cl:1][C:2]1[C:21](I)=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([Cl:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1.C(OC([N:30]1[C:34]([C:35](=[O:39])[N:36]([CH3:38])[CH3:37])=[CH:33][CH:32]=[C:31]1B(O)O)=O)(C)(C)C.C([O-])([O-])=O.[Na+].[Na+].O>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.COCCOC>[Cl:1][C:2]1[C:21]([C:31]2[NH:30][C:34]([C:35](=[O:39])[N:36]([CH3:38])[CH3:37])=[CH:33][CH:32]=2)=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([Cl:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 867026266-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-iodonicotinamideHCID 89907989HCID 89907989, compound

Product 1

HCID 89907993HCID 89907993, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

6-Chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-iodonicotinamide (Stage 48.3, 257 mg, 0.560 mmol), (1-(tert-butoxycarbonyl)-5-(dimethylcarbamoyl)-1H-pyrrol-2-yl)boronic acid (Stage 73.2, 200 mg, 0.709 mmol), Pd(Ph3P)4 (64.7 mg, 0.056 mmol), Na2CO3 (237 mg, 2.240 mmol), water (560 μL) and DME (2.240 mL) were added to a MW vial, which was sealed, evacuated/purged with argon and stirred at 80° C. for 16 h. The RM was diluted with MeOH (1 mL)/DCM (2 mL), treated with Si-Thiol (194 mg, 0.280 mmol), filtered and the filtrate was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (RediSep® Silica gel column, 12 g, cyclohexane-DCM (4:1)/EtOAc, from 5% to 50% EtOAc) to yield the title product as a white solid. UPLC-MS (Condition 3) tR=1.16 min, m/z=469.1 [M+H]+, m/z=513.0 [M+FA+H]−; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.98-3.28 (m, 6H) 6.69-6.75 (m, 1H) 6.76-6.81 (m, 1H) 7.40 (d, J=9.17 Hz, 2H) 7.85-7.93 (m, 2H) 8.62 (d, J=2.32 Hz, 1H) 8.81 (d, J=2.32 Hz, 1H) 10.65 (s, 1H) 11.89 (br. s, 1H).

Workup

  1. customwas sealed
  2. customevacuated/purged with argon
  3. additionThe RM was diluted with MeOH (1 mL)/DCM (2 mL)
  4. filtrationfiltered
  5. customthe filtrate was evaporated off under reduced pressure
  6. customto give a residue which
  7. customwas purified by flash chromatography (RediSep® Silica gel column, 12 g, cyclohexane-DCM (4:1)/EtOAc, from 5% to 50% EtOAc)

Sources & evidence

ORD record
ord-08ba6b5c4963469087a90aa44be5aa1f
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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