Triethylamine → HCID 178425212, compound

HRID 1500986Notes

Reaction equation

HRID 1500986 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][N:19]=2)[C:13]=1[C:24]#[N:25])[C:5](O)=[O:6].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)CC)C.[NH2:57][CH2:58][C:59]1[C:60]([OH:67])=[N:61][C:62]([CH3:66])=[CH:63][C:64]=1[CH3:65]>ClCCl.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][N:19]=2)[C:13]=1[C:24]#[N:25])[C:5]([NH:57][CH2:58][C:59]1[C:60]([OH:67])=[N:61][C:62]([CH3:66])=[CH:63][C:64]=1[CH3:65])=[O:6]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 69672221HCID 69672221, compoundHCID 178425242HCID 178425242, compound

Product 1

HCID 178425212HCID 178425212, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-chloro-4-(2-cyano-3-(pyrimidin-4-yl)phenoxy)benzoic acid (80 mg, 0.23 mmol), 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (130 mg, 0.34 mmol) and triethylamine (70 mg, 0.69 mmol) in dichloromethane (20 mL) was stirred at room temperature for 2 hours. Then 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (42 mmg, 0.28 mmol) was added. The resultant mixture was stirred at room temperature for additional 15 hours. To the reaction mixture, water (30 mL) was added. The mixture was extracted with dichloromethane (30 mL×3). The organic layers were combined and concentrated to give a residue in vacuo. The residue was purified by preparative-HPLC to give 3-Chloro-4-(2-cyano-3-(pyrimidin-4-yl)phenoxy)-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)benzamide I-8 as a white solid (80 mg, 72%). LRMS (M+H+) m/z: calcd 485.13. found 485. HPLC purity (214 nm): 96%. 1H NMR (300 MHz, d6-DMSO): δ 11.49 (s, 1H), 9.39 (s, 1H), 9.04 (d, J=5.1 Hz, 1H), 8.57-8.56 (m, 1H), 8.17 (d, J=1.2 Hz, 1H), 8.05 (d, J=5.1 Hz, 1H), 7.93 (d, J=9 Hz, 1H), 7.83-7.73 (m, 2H), 7.39 (d, J=8.4 Hz, 1H), 7.11 (d, J=8.4 Hz, 1H), 5.87 (s, 1H), 4.30 (d, J=4.8 Hz, 2H), 2.18 (s, 3H), 2.12 (s, 3H).

Workup

  1. extractionThe mixture was extracted with dichloromethane (30 mL×3)
  2. concentrationconcentrated
  3. customto give a residue in vacuo
  4. customThe residue was purified by preparative-HPLC

Sources & evidence

ORD record
ord-49f9f9def62444968d2c9b9ab54e8b76
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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