Acetic Acid → HCID 71115116, compound

HRID 1502445Notes

Reaction equation

HRID 1502445 reaction equation
[F:1][C@H:2]1[CH2:4][C@H:3]1[C:5]([NH:7][C:8]1[N:9]=[CH:10][C:11]2[C:16]([CH:17]=1)=[CH:15][CH:14]=[C:13]([C:18]1[CH:19]=[N:20][C:21]([S:25][CH3:26])=[CH:22][C:23]=1[CH3:24])[CH:12]=2)=[O:6].C(O)(=[O:29])C.OO>O>[F:1][C@H:2]1[CH2:4][C@H:3]1[C:5]([NH:7][C:8]1[N:9]=[CH:10][C:11]2[C:16]([CH:17]=1)=[CH:15][CH:14]=[C:13]([C:18]1[CH:19]=[N:20][C:21]([S:25]([CH3:26])=[O:29])=[CH:22][C:23]=1[CH3:24])[CH:12]=2)=[O:6]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 784Hydrogen Peroxide2×HCID 71115239HCID 71115239, compound

Product 1

HCID 71115116HCID 71115116, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A mixture of (1S,2S)-2-fluoro-N-(7-(4-methyl-6-(methylthio)pyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide (150 mg, 0.3674 mmol) and acetic acid (4.0 mL) was treated with hydrogen peroxide (35 mass % in water, 0.16 mL, 1.8 mmol) at room temperature. After 3 hours, additional hydrogen peroxide was added (35 mass % in water, 0.03 mL; 0.3 mmol). After an additional 30 minutes, the reaction mixture was poured into water (50 mL) and extracted with dichloromethane (2×50 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated. The crude product was purified via preparatory reverse-phase HPLC and lyophilized to yield 63.1 mg (45%) of the title compound. LCMS (ESI): RT (Min)=4.013, M+H=384.2, method=E; 1H NMR (400 MHz, DMSO) δ 1H NMR (400 MHz, DMSO) δ 11.00 (s, 1H), 9.22 (s, 1H), 8.61 (s, 1H), 8.54 (s, 1H), 8.15 (s, 1H), 8.01 (d, J=8.6 Hz, 1H), 7.91 (s, 1H), 7.80 (d, J=8.5 Hz, 1H), 4.96 (m, 1H), 2.86 (s, 3H), 2.46 (s, 3H), 2.35-2.24 (m, 1H), 1.78-1.63 (m, 1H), 1.29-1.12 (m, 1H).

Workup

  1. waitAfter an additional 30 minutes
  2. extractionextracted with dichloromethane (2×50 mL)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified via preparatory reverse-phase HPLC

Sources & evidence

ORD record
ord-b95214ce14ba48b29bb76fd72d25b19e
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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