Acetonitrile → HCID 118195206, compound

HRID 924153Notes

Reaction equation

HRID 924153 reaction equation
Cl[C:2]1[C:7]([C:8]2[C:9]([N:28]3[CH2:32][CH2:31][C@@H:30]([OH:33])[CH2:29]3)=[N:10][CH:11]=[C:12]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([Cl:27])([F:26])[F:25])=[CH:19][CH:18]=3)=[O:15])[CH:13]=2)=[CH:6][C:5]([F:34])=[CH:4][N:3]=1.C[C:36]#[N:37]>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.[C-]#N.[Zn+2].[C-]#N>[Cl:27][C:24]([F:26])([F:25])[O:23][C:20]1[CH:21]=[CH:22][C:17]([NH:16][C:14]([C:12]2[CH:13]=[C:8]([C:7]3[C:2]([C:36]#[N:37])=[N:3][CH:4]=[C:5]([F:34])[CH:6]=3)[C:9]([N:28]3[CH2:32][CH2:31][C@@H:30]([OH:33])[CH2:29]3)=[N:10][CH:11]=2)=[O:15])=[CH:18][CH:19]=1

Participants

6

Reactant 2

HCID 6342AcetonitrileHCID 118195348HCID 118195348, compound

Product 1

HCID 118195206HCID 118195206, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

(R)-2′-Chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5′-fluoro-2-(3-hydroxypyrrolidin-1-yl)-[3,3′-bipyridine]-5-carboxamide (Example 288, 100 mg, 0.195 mmol), Pd(Ph3P)4 (22.51 mg, 0.019 mmol), zinc cyanide (114 mg, 0.974 mmol) were added to a vial, flushed with argon, treated with DMF (2 mL) and stirred for 18 h at 130° C. The solvent was evaporated off under reduced pressure and the residue was purified by preparative SFC (Column NH2, from 16% to 21% in 6 min). The fractions containing product were combined and the solvent was evaporated off under reduced pressure to give a residue which was lyophilized in water/min. vol. MeCN to afford the title product as an off-white powder. UPLC-MS (Condition 3), tR=1.09 min, m/z=504.1/506.1 [M+H]+; 1H-NMR (600 MHz, DMSO-d6) δ ppm 1.70-1.97 (m, 2H) 2.80-2.94 (m, 1H) 3.09-3.23 (m, 1H) 3.23-3.38 (m, 2H) 4.16-4.29 (m, 1H) 4.85-5.02 (m, 1H) 7.35 (d, J=8.47 Hz, 2H) 7.86 (d, J=8.28 Hz, 2H) 8.08-8.37 (m, 2H) 8.86 (d, J=6.96 Hz, 2H) 10.24 (br. s, 1H).

Workup

  1. customflushed with argon
  2. additiontreated with DMF (2 mL)
  3. customThe solvent was evaporated off under reduced pressure
  4. customthe residue was purified by preparative SFC (Column NH2, from 16% to 21% in 6 min)
  5. additionThe fractions containing product
  6. customthe solvent was evaporated off under reduced pressure
  7. customto give a residue which

Sources & evidence

ORD record
ord-3d508c9e14c9462f84f7a4d675ab5725
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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