Diisopropylethylamine → HCID 58267802, compound

HRID 1918139Notes

Reaction equation

HRID 1918139 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[S: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]([S: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[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[N:6]=1)([CH3:2])([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 569536273-(6,7-Dimethoxyquinazolin-4-ylthio)anilineHCID 67159405HCID 67159405, compound

Product 1

HCID 58267802HCID 58267802, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A stirred solution of phenyl 3-tert-butyl-1-cyclohexyl-1H-pyrazol-5-ylcarbamate prepared as described in Example 330A (200 mg, 0.59 mmol), N,N-diisopropylethylamine (67 mg, 0.52 mmol) and 3-(6,7-dimethoxyquinazolin-4-ylthio)aniline (prepared as described in Example 115B) (85 mg, 0.27 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-ylthio)phenyl)urea (52 mg, 18%) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.17 (s, 1H), 8.71 (s, 1H), 8.53 (s, 1H), 7.84 (s, 1H), 7.26-7.55 (m, 5H), 6.06 (s, 1H), 4.00 (s, 6H), 3.94 (m, 1H), 1.62-1.81 (m, 7H), 1.24-1.36 (m, 12H); LC-MS (ESI) m/z 561 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-ef5e9d2311d142c2a4e8988378cb44e3
Source dataset
uspto-grants-2013_12
Patent number
US08618289B2

Reaction notes

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