Methanol → HCID 71555554, compound

HRID 339962Notes

Reaction equation

HRID 339962 reaction equation
[CH3:1][N:2]1[C:6]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[C:12](=[O:16])[N:11]([C@@H:17]([CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=2)[CH2:18][N:19]2C(=O)C4C(=CC=CC=4)C2=O)[CH2:10]3)=[CH:5][CH:4]=[N:3]1.CO.O1CCCC1.NN>>[NH2:19][CH2:18][C@@H:17]([N:11]1[CH2:10][C:9]2[C:13](=[CH:14][CH:15]=[C:7]([C:6]3[N:2]([CH3:1])[N:3]=[CH:4][CH:5]=3)[CH:8]=2)[C:12]1=[O:16])[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=1

Participants

5

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 9321HydrazineHCID 86681454HCID 86681454, compound

Product 1

HCID 71555554HCID 71555554, compoundYield 65.3%

Conditions

Temperature
50 °C

Procedure

The product of Step D (0.72 g, 1.45 mmol) was dissolved in methanol (4 mL, 100 mmol) and tetrahydrofuran (4 mL, 50 mmol). To the resulting solution was added hydrazine (2 mL, 60 mmol). The solution was stirred at 50° C. for 2 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by combi-flash chromatography eluting with MeOH/EtOAc (20-60%). The product was further purified by prep.-LC/MS (pH=10). The purification afforded 345 mg (37.3% yield) of the final product as white solid. LC-MS found: 365.2 (M+1)+; 1H NMR (300 MHz, DMSO-d6) δ ppm: 7.70 (d, J=3.6 Hz, 1H), 7.66 (s, 1H), 7.58 (dd, J1=7.8 Hz, J2=1.2 Hz, 1H), 7.48 (d, J=1.8 Hz, 1H), 7.23 (dd, J1=7.8 Hz, J2=6.3 Hz, 1H), 7.03 (m, 2H), 6.93 (ddd, J1=8.7 Hz, J2=8.4 Hz, J3=2.4 Hz, 1H), 6.45 (d, J=2.1 Hz, 1H), 4.46 (s, 2H), 4.40 (m, 1H), 3.86 (s, 3H), 3.04 (dd, J1=14.4 Hz, J2=5.1 Hz, 1H), 2.88 (dd, J1=14.40 Hz, J2=4.5 Hz, 1H), 2.82 (d, J=6.9 Hz, 2H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was purified by combi-flash chromatography
  3. washeluting with MeOH/EtOAc (20-60%)
  4. customThe product was further purified by prep.-LC/MS (pH=10)
  5. customThe purification

Sources & evidence

ORD record
ord-8170d3c068e54318820b1a5e08033c8b
Source dataset
uspto-grants-2014_11
Patent number
US08895571B2

Reaction notes

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