Diisopropylethylamine → 5-iodo-2-methoxy-4-methyl-N-(1-(pyrimidin-2-yl)cyclopropyl)benzamide

HRID 624309Notes

Reaction equation

HRID 624309 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[C:7]1([NH2:10])[CH2:9][CH2:8]1.[I:11][C:12]1[C:13]([CH3:23])=[CH:14][C:15]([O:21][CH3:22])=[C:16]([CH:20]=1)[C:17](O)=[O:18].C(N(CC)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>[I:11][C:12]1[C:13]([CH3:23])=[CH:14][C:15]([O:21][CH3:22])=[C:16]([CH:20]=1)[C:17]([NH:10][C:7]1([C:2]2[N:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[CH2:9][CH2:8]1)=[O:18]

Participants

6

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 468293605-Iodo-2-methoxy-4-methylbenzoic acidHCID 569656591-(Pyrimidin-2-yl)cyclopropan-1-amine

Product 1

HCID 866916215-iodo-2-methoxy-4-methyl-N-(1-(pyrimidin-2-yl)cyclopropyl)benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 1-(pyrimidin-2-yl)cyclopropanamine (2.00 g, 14.8 mmol) and 5-iodo-2-methoxy-4-methylbenzoic acid (4.75 g, 16.28 mmol) in DMF (8 ml) in a 25 ml RB flask was cooled to 0° C., and then added with N,N-diisopropylethylamine (12.92 ml, 74.0 mmol) followed by HATU (6.75 g, 17.76 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was added ice water and extracted with ethyl acetate (3×25 ml). The combined organic extracts were washed with brine solution, dried over Na2SO4, filtered and concentrated. The crude product was purified by using a silica gel (60-120 mesh) column with 60% ethyl acetate in hexane as an eluent. Yield: 3.2 g, 48%. 1H NMR (400 MHz, CDCl3): δ 8.57 (d, J=4.8 Hz, 2H), 8.52 (s, 1H), 8.47 (s, 1H), 7.03 (t, 1H, J=5.0 Hz), 4.02 (s, 3H), 2.63 (s, 3H), 1.83-1.80 (m, 2H), 1.52-1.49 (m, 2H). LCMS: (ES+) m/z=410 (M+H)+; Column—Ascentis Express C8 (5×2.1 mm-2.7 μm); Mphase A: 2% MeCN-98% H2O-10 mM NH4COOH; Mphase B: 98% MeCN-2% H2O-10 mM NH4COOH; Flow=1 ML/MIN; Time: 0.0, 1.5, 3.2; % A: 100.0, 0.0, 0.0; % B: 0.0, 100.0, 100.0; RT: 1.904 min.

Workup

  1. extractionextracted with ethyl acetate (3×25 ml)
  2. washThe combined organic extracts were washed with brine solution
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified

Sources & evidence

ORD record
ord-40097b21c77a4aa8b636fa920ec6cf93
Source dataset
uspto-grants-2016_04
Patent number
US09303020B2

Reaction notes

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