Dimethylformamide → 3-(3-aminoisoquinolin-7-yl)-N-cyclobutyl-4-methylbenzamide

HRID 1502431Notes

Reaction equation

HRID 1502431 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][C:20]=1[CH3:21])[C:15](O)=[O:16])[CH:6]=2.[CH:22]1([NH2:26])[CH2:25][CH2:24][CH2:23]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.CN(C)C=O>CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][C:20]=1[CH3:21])[C:15]([NH:26][CH:22]1[CH2:25][CH2:24][CH2:23]1)=[O:16])[CH:6]=2

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 75645CyclobutylamineHCID 81531DiisopropylethylamineHCID 11038641((7-Azabenzotriazol-1-YL)oxy)tris(pyrrolidino)phosphonium hexafluorophosphateHCID 679748773-(3-Aminoisoquinolin-7-yl)-4-methylbenzoic acid

Product 1

HCID 679747473-(3-aminoisoquinolin-7-yl)-N-cyclobutyl-4-methylbenzamideYield 8.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-(3-aminoisoquinolin-7-yl)-4-methylbenzoic acid (43.0 mg; 0.155 mmol), cyclobutylamine (27 μL; 0.310 mmol), (7-azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (129.5 mg; 0.2384 mmol), N,N-diisopropylethylamine (0.1 mL; 0.6 mmol), 4-(dimethylamino)pyridine (0.1 equiv.; 0.0155 mmol) and N,N-dimethylformamide (2.0 mL; 26 mmol) was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, washed with water (2×) and brine, dried over magnesium sulfate, and filtered through a plug of silica gel, rinsing with additional ethyl acetate. The filtrate was evaporated in vacuo to yield 53.6 mg crude product. 20.2 mg of crude product was purified via preparatory reverse-phase HPLC and lyophilized to yield 4.2 mg of the title compound. LCMS (ESI): RT (Min)=2.88, M+H=327.3, method=H; 1H NMR (400 MHz, DMSO) δ 8.87 (s, 1H), 8.56 (d, J=8.0 Hz, 1H), 7.82-7.74 (m, 3H), 7.60 (d, J=8.6 Hz, 1H), 7.49 (d, J=8.6 Hz, 1H), 7.39 (d, J=7.9 Hz, 1H), 6.67 (s, 1H), 5.95 (s, 2H), 4.50-4.34 (m, 1H), 2.31 (s, 3H), 2.26-2.13 (m, 2H), 2.06 (m, 2H), 1.73-1.57 (m, 2H).

Workup

  1. washwashed with water (2×) and brine
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered through a plug of silica gel
  4. washrinsing with additional ethyl acetate
  5. customThe filtrate was evaporated in vacuo
  6. customto yield 53.6 mg crude product
  7. custom20.2 mg of crude product was purified via preparatory reverse-phase HPLC

Sources & evidence

ORD record
ord-18a02fc01f2c4061b2f724b2923170c7
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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