Isopropylamine → HCID 57496316, compound

HRID 1958399Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-[1-(2-fluoro-4-iodo-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester (263 mg, 0.50 mmol), isopropylamine (450 μL, 5.0 mmol), L-proline (86 mg, 0.75 mmol), copper iodide (95 mg, 0.50 mmol) and potassium carbonate (207 mg, 1.50 mmol) in DMSO (4.0 mL) was heated under microwave irradiation for 50 min at 100° C. The crude mixture was concentrated in vacuo and purified by HPLC to provide Compound A230 as a white solid (80 mg, 35%). 1H NMR (CDCl3, 400 MHz) δ 1.20 (d, 6H), 1.26 (d, 6H), 1.75-1.88 (m, 2H), 1.98-2.09 (m, 2H), 3.28-3.37 (m, 2H), 3.55-3.63 (m, 1H), 3.78-3.87 (m, 2H), 4.88 (h, 1H), 5.55 (h, 1H), 6.90-7.08 (m, 2H), 7.44-7.50 (m, 1H), 8.17 (s, 1H), 8.53 (s, 1H). Exact mass calculated for C23H29FN6O3 456.51, found 457.3 (MH+).

Workup

concentrationThe crude mixture was concentrated in vacuo
custompurified by HPLC

Sources & evidence

ORD record: ord-40c8f34e801149f6bbfbc1c65502509b
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08410119B2

Reaction notes

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