Diisopropylethylamine → HCID 58267929, compound

HRID 871490Notes

Reaction equation

HRID 871490 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:12])[O-])=[CH:5][C:4]=1[C:13]([F:16])([F:15])[F:14].[CH3:17][O:18][C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][C:28]=1[O:29][CH2:30][CH2:31][O:32][CH3:33])[N:25]=[CH:24][N:23]=[C:22]2[O:34][C:35]1[CH:36]=[C:37]([CH:39]=[CH:40][CH:41]=1)[NH2:38].C(N(C(C)C)CC)(C)C>CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([NH:38][C:37]2[CH:39]=[CH:40][CH:41]=[C:35]([O:34][C:22]3[C:21]4[C:26](=[CH:27][C:28]([O:29][CH2:30][CH2:31][O:32][CH3:33])=[C:19]([O:18][CH3:17])[CH:20]=4)[N:25]=[CH:24][N:23]=3)[CH:36]=2)=[O:12])=[CH:5][C:4]=1[C:13]([F:16])([F:15])[F:14]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 668758053-(6-Methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)anilineHCID 86653517HCID 86653517, compound

Product 1

HCID 58267929HCID 58267929, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

According to the procedure for Example 138B, 4-methoxy-3-(trifluoromethyl)phenylcarbamate described in Example 138A (104 mg, 0.34 mmol) was reacted with 3-(6-methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)aniline described in Example 117B (100 mg, 0.28 mmol). To this solution was added diisopropylethyl amine (74 μL, 0.42 mmol) and DMAP (20.0 mg, 0.16 mmol). The reaction was concentrated to dryness and partitioned between water and dichloromethane, and extracted twice. The combined extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude oil was purified by silica gel chromatography (methanol/dichloromethane 0-5%) to give 1-(4-methoxy-3-(trifluoromethyl)phenyl)-3-(3-(6-methoxy-7-(2-methoxyethoxy)quinazolin-4-yloxy)phenyl)urea as a white solid (18.6 mg, 10% yield). 1H (DMSO-d6) 8.90 (s, 1H), 8.80 (s, 1H), 8.60 (s, 1H), 7.85 (s, 1H), 7.60 (m, 3H), 7.40 (m, 2H), 7.25 (m, 2H), 6.90 (d, 1H), 4.35 (m, 2H), 3.99 (s, 3H), 3.80 (s, 3H), 3.75 (m, 2H), 3.30 (s, 3H). LCMS (ESI) m/z 559 (M+H)+.

Workup

  1. concentrationThe reaction was concentrated to dryness
  2. custompartitioned between water and dichloromethane
  3. extractionextracted twice
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude oil was purified by silica gel chromatography (methanol/dichloromethane 0-5%)

Sources & evidence

ORD record
ord-84d91ac5afb54c7889494898a298bfdc
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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