Hydrazine → HCID 59458804, compound

HRID 238840Notes

Reaction equation

O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH:12]([C:46]([F:49])([F:48])[F:47])[CH2:13][C:14]([NH:16][C@@:17]([C:32]1[CH:37]=[C:36]([O:38][C:39]([F:44])([F:43])[CH:40]([F:42])[F:41])[CH:35]=[C:34]([F:45])[CH:33]=1)([C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:15].NN>CO>[NH2:3][CH:12]([C:46]([F:49])([F:48])[F:47])[CH2:13][C:14]([NH:16][C@@:17]([C:32]1[CH:37]=[C:36]([O:38][C:39]([F:44])([F:43])[CH:40]([F:42])[F:41])[CH:35]=[C:34]([F:45])[CH:33]=1)([C:25]1[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=1)[CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:15]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 3-(1,3-dioxoisoindolin-2-yl)-4,4,4-trifluoro-N—((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)butanamide (Example 325, 30 mg, 0.04 mmol) in MeOH (1 mL) was added hydrazine (0.03 mL, 1 mmol) and the reaction mixture was heated at 50° C. for 4 h. The reaction mixture was purified by preparative HPLC (Axia luna column, 30×75 mm, 10-100% ACN/H2O with 0.1% TFA over 10 min, flow rate 40 mL/min, monitoring at 220 nm) to yield 3-amino-4,4,4-trifluoro-N—((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)butanamide (Example 326) as white solid (7 mg, 24% yield). LCMS: RT=3.62 min [M+H] 565.2 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm). 1H NMR (400 MHz, CDCl3) δ ppm 7.34 (1H, d, J=17.94 Hz), 7.13-7.24 (3H, m), 6.96-7.11 (4H, m), 6.82-6.92 (3H, m), 6.62 (2H, d, J=7.83 Hz), 5.86 (1H, t, J=1.77 Hz), 3.88 (1H, t, J=12.63 Hz), 3.75-3.84 (1H, m), 3.70 (1H, d, J=13.14 Hz), 2.82-2.93 (1H, m), 2.77 (1H, m).

Workup

customThe reaction mixture was purified by preparative HPLC (Axia luna column, 30×75 mm, 10-100% ACN/H2O with 0.1% TFA over 10 min, flow rate 40 mL/min, monitoring at 220 nm)

Sources & evidence

ORD record: ord-d8bbb257acc64ef385f5a11840de99b5
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08642576B2

Reaction notes

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