Water → HCID 71293526, compound

HRID 1402562Notes

Reaction equation

HRID 1402562 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[C:17]([O:19][C:20]3[CH:25]=[CH:24][C:23]([NH:26][C:27]([NH:29][C:30]4[CH:35]=[C:34]([CH3:36])[CH:33]=[CH:32][C:31]=4[F:37])=[O:28])=[C:22]([F:38])[CH:21]=3)[CH:16]=[CH:15][N:14]=2)[NH:10][CH:9]=1)=[O:7].C(N(CC)C(C)C)(C)C.Br[CH2:49][C:50]([O:52][CH3:53])=[O:51].[OH2:54].C1[CH2:59][O:58][CH2:57][CH2:56]1>>[F:38][C:22]1[CH:21]=[C:20]([CH:25]=[CH:24][C:23]=1[NH:26][C:27]([NH:29][C:30]1[CH:35]=[C:34]([CH3:36])[CH:33]=[CH:32][C:31]=1[F:37])=[O:28])[O:19][C:17]1[CH:16]=[CH:15][N:14]=[C:13]([C:11]2[NH:10][CH:9]=[C:8]([C:6]([NH:5][CH2:4][CH2:3][CH2:2][N:1]([CH2:56][C:57]([O:58][CH3:59])=[O:54])[CH2:49][C:50]([O:52][CH3:53])=[O:51])=[O:7])[CH:12]=2)[CH:18]=1

Participants

6

Reactant 5

HCID 962WaterHCID 8028TetrahydrofuranHCID 60984Methyl bromoacetateHCID 81531DiisopropylethylamineHCID 71293578HCID 71293578, compound

Product 1

HCID 71293526HCID 71293526, compound

Conditions

Temperature
55 °C

Procedure

To a stirred suspension of N-(3-aminopropyl)-5-{4-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxamide (240 mg, 0.46 mmol) in 10 ml of anhydrous THF were added N,N-diisopropylethylamine (1 ml, 5.6 mmol) and methyl bromoacetate (300 mg, 2.0 mmol). The mixture was heated at 55° C. for 3 hours and poured into 100 ml of water with vigorous stirring. The precipitates were filtered and dried in vacuo to give the crude, which was purified by silica gel chromatography eluting with 3˜4% of MeOH in CHCl3 to afford dimethyl 2,2′-[(3-{[(5-{4-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrol-3-yl)carbonyl]amino}propyl)imino]diacetate as white solid. Yield: 160 mg, 52%.

Workup

  1. filtrationThe precipitates were filtered
  2. customdried in vacuo
  3. customto give the crude, which
  4. customwas purified by silica gel chromatography
  5. washeluting with 3˜4% of MeOH in CHCl3

Sources & evidence

ORD record
ord-e599d2fcf26b4fa3be40ee0265d06067
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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