Cyclohexylamine → N1-(4-(2-aminopyridin-4-yloxy)-3-fluorophenyl)-N3-cyclohexylmalonamide, hydrochloride salt

HRID 2374065Notes

Reaction equation

[ClH:1].NC(=O)[C@@H]([NH:11][C:12](=[O:32])[CH2:13][C:14]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][C:24]2[CH:29]=[CH:28][N:27]=[C:26]([NH2:30])[CH:25]=2)=[C:19]([F:31])[CH:18]=1)=[O:15])C1C=CC=CC=1.[CH:34]1(N)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>>[ClH:1].[NH2:30][C:26]1[CH:25]=[C:24]([O:23][C:20]2[CH:21]=[CH:22][C:17]([NH:16][C:14](=[O:15])[CH2:13][C:12]([NH:11][CH:34]3[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]3)=[O:32])=[CH:18][C:19]=2[F:31])[CH:29]=[CH:28][N:27]=1

Participants

Reactant 2

HCID 7965Cyclohexylamine

HCID 131727213(S)-N-(2-amino-2-oxo-1-phenylethyl)-N3(4-(2-aminopyridin-4-yloxy)-3-fluorophenyl)malonamide, hydrochloride salt2×

Product 1

HCID 131727216N1-(4-(2-aminopyridin-4-yloxy)-3-fluorophenyl)-N3-cyclohexylmalonamide, hydrochloride saltYield 52%

Procedure

3-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenylamino)-3-oxopropanoic acid (Compound C of Example 102, 30 mg, 0.10 mmol) was coupled with cyclohexanamine (Aldrich, 20 mg, 0.2 mmol) in a manner similar to that which is described in Step C of Example 1 to give N1-(4-(2-aminopyridin-4-yloxy)-3-fluorophenyl)-N3-cyclohexylmalonamide, hydrochloride salt (22 mg, 52% yield). 1H NMR (DMSO-d6) δ 14.00 (s, 1H), 10.72 (s, 1H), 8.10 (d, 1H, J=7.0 Hz), 7.97 (d, 1H, J=7.0 Hz), 7.88 (m, 3H), 7.44 (m, 2H), 6.70 (m, 1H), 6.14 (d, 1H, J=2.0 Hz), 3.54 (m, 1H), 3.27 (s, 2H), 1.66-1.75 (m, 4H), 1.52 (m, 1H), 1.15-1.25 (m, 5H); MS(ESI+) m/z 387.32 (M+H)+.

Sources & evidence

ORD record: ord-eca8a4afc32b45b4802dbf0c71eedfbb
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07459562B2

Reaction notes

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