Diisopropylethylamine → HCID 59451616, compound

HRID 1874812Notes

Reaction equation

HRID 1874812 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([Cl:19])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.CC1(C)[O:26][C@@H:25]([CH2:27][CH2:28][O:29][C:30]2[CH:31]=[C:32]3[C:36](=[CH:37][CH:38]=2)[NH:35][C:34]([C:39](O)=[O:40])=[CH:33]3)[CH2:24][O:23]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O.CCOC(C)=O>[Cl:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:2][NH:1][C:39]([C:34]2[NH:35][C:36]3[C:32]([CH:33]=2)=[CH:31][C:30]([O:29][CH2:28][CH2:27][C@H:25]([OH:26])[CH2:24][OH:23])=[CH:38][CH:37]=3)=[O:40])=[C:4]([F:20])[C:5]=1[O:10][C:11]1[CH:12]=[C:13]([C:14]#[N:15])[CH:16]=[C:17]([Cl:19])[CH:18]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 68483702HCID 68483702, compound

Product 1

HCID 59451616HCID 59451616, compoundYield 42.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (25.0 mg, 0.080 mmol), 5-({2-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl}oxy)-1H-indole-2-carboxylic acid (24.53 mg, 0.080 mmol) and DIPEA (0.014 mL, 0.080 mmol) in DMF (1 mL) was added HATU (30.6 mg, 0.080 mmol). After 2 h the reaction mixture was poured into EtOAc and water. The organic layer was separated, dried over MgSO4 and the solvent evaporated. The residue was diluted to 2 mL with MeOH. Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA) to afford the title compound (0.019 g, 42%) as a white solid. 1H NMR (400 MHz, Acetone-d6): δ ppm 10.67 (br. s., 1H), 8.31 (t, 1H), 7.60 (t, 1H), 7.46 (d, 1H), 7.40-7.42 (m, 1H), 7.38-7.40 (m, 1H), 7.34-7.38 (m, 2H), 7.07 (d, 1H), 7.04 (d, 1H), 6.88 (dd, 1H), 4.67 (d, 2H), 4.04-4.17 (m, 2H), 3.82-3.91 (m, 1H), 3.51-3.58 (m, 1H), 3.43-3.50 (m, 1H), 1.92-2.01 (m, 1H), 1.73-1.84 (m, 1H). LCMS m/z 558.0 (M+1).

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over MgSO4
  3. customthe solvent evaporated
  4. additionThe residue was diluted to 2 mL with MeOH
  5. customPurification

Sources & evidence

ORD record
ord-4fd345dde78141b7913ddf42b1e6ba7c
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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