Piperidin-4-ol → HCID 71765393, compound

HRID 2203243Notes

Reaction equation

HRID 2203243 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:13]3[CH:21]=[C:20]4[C:16]([CH:17]=[N:18][NH:19]4)=[CH:15][C:14]=3[CH3:22])[CH:8]=[C:9](F)[CH:10]=2)[N:5]=[N:4][C:3]=1[C:23]([NH2:25])=[O:24].CCN(C(C)C)C(C)C.[NH:35]1[CH2:40][CH2:39][CH:38]([OH:41])[CH2:37][CH2:36]1>CC(N(C)C)=O>[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:13]3[CH:21]=[C:20]4[C:16]([CH:17]=[N:18][NH:19]4)=[CH:15][C:14]=3[CH3:22])[CH:8]=[C:9]([N:35]3[CH2:40][CH2:39][CH:38]([OH:41])[CH2:37][CH2:36]3)[CH:10]=2)[N:5]=[N:4][C:3]=1[C:23]([NH2:25])=[O:24]

Participants

5

Reactant 3

HCID 79341Piperidin-4-olHCID 81531DiisopropylethylamineHCID 71765394HCID 71765394, compound

Product 1

HCID 71765393HCID 71765393, compoundYield 24.4%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
140 °C

Procedure

The mixture of 4-amino-6-fluoro-8-(5-methyl-1H-indazol-6-yl)cinnoline-3-carboxamide (200 mg, 0.59 mmol), DIPEA (1000 mg), piperidin-4-ol (573 mg) and DMA (4 mL) was heated at 140° C. in a microwave under N2 for 3 h. The mixture was cooled, concentrated and purified directly with prep-HPLC to give the title compound as solid (60 mg, yield=24%). 1H NMR (400 MHz, DMSO-d6): δ 12.93 (1H, s), 8.27 (1H, s), 8.02 (1H, s), 7.60 (1H, s), 7.48-7.47 (3H, m), 7.35 (1H, s), 4.74 (1H, d, J=4.4 Hz), 3.89-3.86 (2H, m), 3.75-3.72 (m, 1H), 3.17-3.12 (2H, m), 2.00 (3H, s), 1.87-1.84 (2H, m), 1.53-1.49 (2H, m); LC-MS (5-95% ACN in H2O gradient with 0.02% NH4OAc, tR 2.809 minutes); ESI+APCI m/z [M+H]+ 418.

Workup

  1. temperatureThe mixture was cooled
  2. concentrationconcentrated
  3. custompurified directly with prep-HPLC

Sources & evidence

ORD record
ord-f1b352f9317648b78a1c559012799e50
Source dataset
uspto-grants-2016_06
Patent number
US09365566B2

Reaction notes

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