Sodium Hydroxide → HCID 59394137, compound

HRID 450252Notes

Reaction equation

HRID 450252 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=1)=[O:12])[CH:6]=[CH:5]2.OC1C=C2C(=CC=1)N(C(NC1C=CC=C(C(F)(F)F)C=1)=O)CC2.[OH-].[Na+].[Cl:49][C:50]1[N:55]=[C:54](Cl)[CH:53]=[CH:52][N:51]=1>CC(C)=O.O>[Cl:49][C:50]1[N:55]=[C:54]([O:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[N:7]([C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:21])[F:22])[CH:15]=2)=[O:12])[CH:6]=[CH:5]3)[CH:53]=[CH:52][N:51]=1

Participants

7

Reactant 4

HCID 14798Sodium Hydroxide2×HCID 775312,4-DichloropyrimidineHCID 59394559HCID 59394559, compoundHCID 59394752HCID 59394752, compound

Product 1

HCID 59394137HCID 59394137, compound

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

A mixture of 5-hydroxy-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide and 5-hydroxy-N-(3-(trifluoromethyl)phenyl)indoline-1-carboxamide (6:4) (3 g) is mixed with sodium hydroxide (0.45 g, 11.2 mmol) and 2,4-dichloropyrimidine (1.68 g, 11.2 mmol) in 50 mL of acetone and 50 mL of water at 0° C. and stirred for 1.5 h. Additional sodium hydroxide (0.075 g, 1.88 mmol) and (0.279 g, 1.88 mmol) are added. After additional 30 min stirring the reaction is concentrated, diluted with EtOAc, washed with water and brine before the organic layer is dried over sodium sulfate and concentrated. The residue is separated via FCC (5-50% EtOAc in heptane) to give 5-(2-chloropyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide. 1H NMR (400 MHz, CDCl3) δ ppm 8.45 (d, J=5.7 Hz, 1H), 8.24 (d, J=9.0 Hz, 1H), 7.86 (s, 1H), 7.78 (d, J=8.2 Hz, 1H), 7.60 (d, J=3.7 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 7.45-7.50 (m, 2H), 7.42 (d, J=2.1 Hz, 1H), 7.15 (dd, J=8.9, 2.3 Hz, 1H), 6.82 (d, J=5.7 Hz, 1H), 6.73 (dd, J=3.7, 0.6 Hz, 1H).

Workup

  1. stirringAfter additional 30 min stirring the reaction
  2. concentrationis concentrated
  3. additiondiluted with EtOAc
  4. washwashed with water and brine before the organic layer
  5. dry with materialis dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue is separated via FCC (5-50% EtOAc in heptane)

Sources & evidence

ORD record
ord-20695f77a78c4a1498c871028f339992
Source dataset
uspto-grants-2013_07
Patent number
US08486954B2

Reaction notes

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