Hydrochloric Acid → Taladegib hydrochloride

HRID 1466223Notes

Reaction equation

HRID 1466223 reaction equation
[F:1][C:2]1[CH:33]=[CH:32][C:5]([C:6]([N:8]([CH3:31])[CH:9]2[CH2:14][CH2:13][N:12]([C:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:18]([C:25]4[N:29]([CH3:30])[N:28]=[CH:27][CH:26]=4)=[N:17][N:16]=3)[CH2:11][CH2:10]2)=[O:7])=[C:4]([C:34]([F:37])([F:36])[F:35])[CH:3]=1.[ClH:38].C(OCC)C>ClCCl>[ClH:38].[F:1][C:2]1[CH:33]=[CH:32][C:5]([C:6]([N:8]([CH3:31])[CH:9]2[CH2:14][CH2:13][N:12]([C:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:18]([C:25]4[N:29]([CH3:30])[N:28]=[CH:27][CH:26]=4)=[N:17][N:16]=3)[CH2:11][CH2:10]2)=[O:7])=[C:4]([C:34]([F:36])([F:37])[F:35])[CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 49848070Taladegib

Product 1

HCID 67285497Taladegib hydrochlorideYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dissolve 4-fluoro-N-methyl-N-(1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-yl)-2-(trifluoromethyl)benzamide (7.13 g, 13.91 mmol) in dichloromethane (100 mL) and add excess 1 N HCl in diethyl ether (30 mL, 30 mmol). Remove the solvents under reduced pressure to provide the title compound (7.05 g, 92%). ES/MS m/z 513.0 (M+1). NMR showed a 2:1 mixture of amide rotamers. Major rotamer; 1H NMR (400 MHz, DMSO-d6): δ 8.34 (m, 1H), 8.26 (m, 2H), 7.95 (m, 1H), 7.75 (m, 1H), 7.64 (m, 2H), 7.55 (m, 1H), 6.72 (d, 1H, J=2 Hz), 5.15 (br, 1H), 4.71 (m, 1H), 4.22 (m, 2H), 3.84 (s, 3H), 3.48 (m, 2H), 2.65 (s, 3H), 2.19 (m, 2H), 1.89 (m, 2H). Minor rotamer; 1H NMR (400 MHz, DMSO-d6): δ 8.27 (m, 1H), 8.24 (m, 2H), 7.94 (m, 1H), 7.73 (m, 1H), 7.63 (m, 3H), 6.70 (d, 1H, J=2 Hz), 5.15 (br, 1H), 4.71 (m, 1H), 4.07 (m, 2H), 3.81 (s, 3H), 3.16 (m, 2H), 2.92 (s, 3H), 1.90 (m, 2H), 1.62 (m 2H).

Workup

  1. customRemove the solvents under reduced pressure

Sources & evidence

ORD record
ord-9cc8142793fa4d9ea328cc33e2069b1d
Source dataset
uspto-grants-2015_04
Patent number
US09000023B2

Reaction notes

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