Isopropylamine → HCID 59856881, compound

HRID 1174744Notes

Reaction equation

[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([C:20]#[N:21])=[C:18]([NH:22][C:23]3[CH:28]=[CH:27][C:26](I)=[CH:25][C:24]=3[F:30])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[CH:31]([NH2:34])([CH3:33])[CH3:32].N1CCC[C@H]1C(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu](I)I>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([C:20]#[N:21])=[C:18]([NH:22][C:23]3[CH:28]=[CH:27][C:26]([NH:34][CH:31]([CH3:33])[CH3:32])=[CH:25][C:24]=3[F:30])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

4-[5-Cyano-6-(2-fluoro-4-iodo-phenylamino)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester (250 mg, 0.48 mmol), isopropylamine (408 μL, 4.8 mmol), proline (99 mg, 0.86 mmol), copper iodide (92 mg, 0.48 mmol) and potassium carbonate (152 mg, 1.1 mmol) were mixed together in DMSO (4 mL). The reaction vessel was heated in a microwave at 80° C. for 1.0 hour. Progress of the reaction was monitored by TLC and LCMS. Purification by HPLC afforded compound A63 as a white solid (50 mg, 23%). 1H NMR (CDCl3, 400 MHz) δ 8.37 (s, 1H), 7.99 (t, 1H), 7.12 (s, 1H), 6.93 (t, 2H), 5.38 (h, 1H), 4.87 (h, 1H), 3.72 (m, 2H), 3.52 (m, 1H), 1.91 (m, 2H), 1.77 (m, 2H), 1.92 (m, 2H), 1.26 (d, 6H), 1.13 (d, 6H). Exact mass calculated for C23H29FN6O3 456.51, found 457.1 (MH+).

Workup

customPurification by HPLC

Sources & evidence

ORD record: ord-490a68f5e7aa4cf2a8fcbb38f90e69c8
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07838525B2

Reaction notes

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