Diisopropylethylamine → HCID 56954223, compound

HRID 1918138Notes

Reaction equation

HRID 1918138 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:19])OC2C=CC=CC=2)[N:7]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.[CH3:35][O:36][C:37]1[CH:38]=[C:39]2[C:44](=[CH:45][C:46]=1[O:47][CH3:48])[N:43]=[CH:42][N:41]=[C:40]2[O:49][C:50]1[CH:51]=[C:52]([CH:54]=[CH:55][CH:56]=1)[NH2:53]>C1COCC1>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:53][C:52]2[CH:54]=[CH:55][CH:56]=[C:50]([O:49][C:40]3[C:39]4[C:44](=[CH:45][C:46]([O:47][CH3:48])=[C:37]([O:36][CH3:35])[CH:38]=4)[N:43]=[CH:42][N:41]=3)[CH:51]=2)=[O:19])[N:7]([CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]2)[N:6]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilineHCID 67159405HCID 67159405, compound

Product 1

HCID 56954223HCID 56954223, compoundYield 38.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of phenyl 3-tert-butyl-1-cyclohexyl-1H-pyrazol-5-Ylcarbamate (200 mg), N,N-Diisopropylethylamine (67 mg, 0.52 mmol) and 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline (prepared as described in Example 113A) (80 mg, 0.26 mmol) in THF (1.0 mL) was heated at 60° C. for 15 h. After cooling to rt, the reaction solution was partitioned between dichloromethane and a saturated aqueous solution of sodium carbonate. The organic phase was separated and concentrated under reduced pressure. The crude product was purified via silica gel column chromatography (eluting with a gradient of 40:1 to 20:1 dichloromethane:methanol) then reverse-phase preparative HPLC to afford 1-(3-tert-butyl-1-cyclohexyl-1H-pyrazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea (55 mg, 10% over two steps) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.10 (s, 1H), 8.57 (s, 1H), 8.47 (s, 1H), 7.57-7.60 (m, 2H), 7.37-7.41 (m, 2H), 7.24 (m, 1H), 6.93 (m, 1H), 6.01 (s, 1H), 4.00 (s, 3H), 3.99 (s, 3H), 3.94 (m, 1H), 1.62-1.82 (m, 8H), 1.24-1.35 (m, 2H), 1.24 (s, 9H); LC-MS (ESI) m/z 545 (M+H)+.

Workup

  1. customthe reaction solution was partitioned between dichloromethane
  2. customThe organic phase was separated
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified via silica gel column chromatography (
  5. washeluting with a gradient of 40:1 to 20:1 dichloromethane

Sources & evidence

ORD record
ord-a69072ce9b4945aab8e3c9584d19923b
Source dataset
uspto-grants-2013_12
Patent number
US08618289B2

Reaction notes

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