Diisopropylethylamine → HCID 25099555, compound

HRID 2381920Notes

Reaction equation

HRID 2381920 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([CH3:14])[C:11]([C:15]([OH:17])=O)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.C1CN([P+](ON2N=NC3C=CC=NC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[Br:60][C:61]1[CH:62]=[C:63]2[C:67](=[CH:68][CH:69]=1)[N:66]([NH2:70])[CH:65]=[CH:64]2>C(Cl)Cl.O.CCOC(C)=O>[Br:60][C:61]1[CH:62]=[C:63]2[C:67](=[CH:68][CH:69]=1)[N:66]([NH:70][C:15]([C:11]1[C:12]([CH3:14])=[N:13][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:9][CH:10]=1)=[O:17])[CH:65]=[CH:64]2

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 10584602HCID 10584602, compoundHCID 11038641((7-Azabenzotriazol-1-YL)oxy)tris(pyrrolidino)phosphonium hexafluorophosphateHCID 617025872-(3-Fluorophenyl)-4-methylpyrimidine-5-carboxylic acid

Product 1

HCID 25099555HCID 25099555, compoundYield 24.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (596 mg, 2.57 mmol), PyAOP (2.63 mmol), and DIPEA (830 μL, 4.75 mmol) in DCM (20 mL) is stirred at rt under N2 for 10 min. 5-Bromoindol-1-ylamine (500 mg, 2.37 mmol) is added. The resulting mixture is stirred at rt overnight. The mixture is portioned between EtOAc and water. The organic phase is separated, washed with saturated aqueous NaHCO3, water and brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 2% MeOH in DCM to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (5-bromo-indol-1-yl)-amide (246 mg, 24%) as a solid. MS: 425 (M) & 427 (M+2). 1H NMR (300 MHz, DMSO-d6): δ 12.02 (s, 1H), 9.24 (s, 1H), 8.34 (d, 1H), 8.20-8.15 (m, 1H), 7.84 (d, 1H), 7.68-7.61 (m, 1H), 7.59 (d, 1H), 7.50-7.43 (m, 2H), 7.35 (dd, 1H), 6.57 (dd, 1H), 2.78 (s, 3H).

Workup

  1. customThe organic phase is separated
  2. washwashed with saturated aqueous NaHCO3, water and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by silica gel chromatography
  7. washeluting with 2% MeOH in DCM

Sources & evidence

ORD record
ord-e8ca09b0e2654ee1b83793de40624ed4
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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