Dimethylformamide → cyclopropane-1,1-dicarboxylic acid {3-fluoro-4-[6-(2-morpholin-4-yl-ethylcarbamoyl)-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-phenyl}-amide(4-fluoro-phenyl)-amide

HRID 1011302Notes

Reaction equation

HRID 1011302 reaction equation
[F:1][C:2]1[CH:28]=[C:27]([NH:29][C:30]([C:32]2([C:35](=[O:44])[NH:36][C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)[CH2:34][CH2:33]2)=[O:31])[CH:26]=[CH:25][C:3]=1[O:4][C:5]1[C:6]2[CH:13]=[C:12]([C:14](O)=[O:15])[N:11]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:7]=2[N:8]=[CH:9][N:10]=1.[N:45]1([CH2:51][CH2:52][NH2:53])[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C=O)C>C(OCC)(=O)C>[F:43][C:40]1[CH:41]=[CH:42][C:37]([NH:36][C:35]([C:32]2([C:30]([NH:29][C:27]3[CH:26]=[CH:25][C:3]([O:4][C:5]4[C:6]5[CH:13]=[C:12]([C:14](=[O:15])[NH:53][CH2:52][CH2:51][N:45]6[CH2:50][CH2:49][O:48][CH2:47][CH2:46]6)[N:11]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:23])([CH3:22])[CH3:24])[C:7]=5[N:8]=[CH:9][N:10]=4)=[C:2]([F:1])[CH:28]=3)=[O:31])[CH2:33][CH2:34]2)=[O:44])=[CH:38][CH:39]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 4082852-MorpholinoethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 589380284-(2-fluoro-4-{[1-(4-fluoro-phenylcarbamoyl)-cyclopropanecarbonyl]-amino}-phenoxy)-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid

Product 1

HCID 58938029cyclopropane-1,1-dicarboxylic acid {3-fluoro-4-[6-(2-morpholin-4-yl-ethylcarbamoyl)-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-phenyl}-amide(4-fluoro-phenyl)-amideYield 83.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a round bottom flask equipped with a magnetic stir bar was added 4-(2-Fluoro-4-{[1-(4-fluoro-phenylcarbamoyl)-cyclopropanecarbonyl]-amino}-phenoxy)-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (0.05 g, 0.08 mmol, 1.0 eq.), 2-Morpholin-4-yl-ethylamine (0.016 ml, 0.12 mmol, 1.5 eq), HATU (0.076 g, 0.2 mmol, 2.5 eq), TEA (0.033 ml, 0.24 mmol, 3.0 eq), and dry DMF (5 ml). The resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate, washed with (2×) H2O (50 ml), sat'd NaHCO3 (2×), 5% LiCl (3×), sat'd NaCl (1×), dried (Na2SO4), and concentrated in vacuo, giving cyclopropane-1,1-dicarboxylic acid {3-fluoro-4-[6-(2-morpholin-4-yl-ethylcarbamoyl)-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-phenyl}-amide(4-fluoro-phenyl)-amide as a cream solid (0.049 g, 83% yield). MS (ESI) for C36H43F2N7O6Si: 736 (MH+).

Workup

  1. customTo a round bottom flask equipped with a magnetic stir bar
  2. washwashed with (2×) H2O (50 ml), sat'd NaHCO3 (2×), 5% LiCl (3×), sat'd NaCl (1×)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fd952d59f2494a25aef584fe068de221
Source dataset
uspto-grants-2011_07
Patent number
US07977345B2

Reaction notes

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