Dimethylformamide → 4-(2-fluoro-4-{[1-(4-fluoro-phenylcarbamoyl)-cyclopropanecarbonyl]-amino}-phenoxy)-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid ethyl ester

HRID 1011300Notes

Reaction equation

HRID 1011300 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:15]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:9]2[N:10]=[CH:11][N:12]=[C:13](Cl)[C:8]=2[CH:7]=1)=[O:5])[CH3:2].[F:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32]([C:34]2([C:37]([OH:39])=O)[CH2:36][CH2:35]2)=[O:33])=[CH:27][CH:26]=1.CN(C(ON1N=[N:55][C:50]2[CH:51]=[CH:52]C=N[C:49]1=2)=[N+](C)C)C.[F:57][P-](F)(F)(F)(F)F.CN(C=O)C.C([O:72][CH2:73][CH3:74])(=O)C>>[CH2:1]([O:3][C:4]([C:6]1[N:15]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:9]2[N:10]=[CH:11][N:12]=[C:13]([O:72][C:73]3[CH:74]=[CH:49][C:50]([NH:55][C:37]([C:34]4([C:32](=[O:33])[NH:31][C:28]5[CH:27]=[CH:26][C:25]([F:24])=[CH:30][CH:29]=5)[CH2:35][CH2:36]4)=[O:39])=[CH:51][C:52]=3[F:57])[C:8]=2[CH:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210815301-[(4-Fluorophenyl)carbamoyl]cyclopropanecarboxylic AcidHCID 589380134-chloro-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid ethyl ester

Product 1

HCID 589380244-(2-fluoro-4-{[1-(4-fluoro-phenylcarbamoyl)-cyclopropanecarbonyl]-amino}-phenoxy)-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid ethyl esterYield 53%

Procedure

To a round bottom flask equipped with a magnetic stir bar was added 4-chloro-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (0.178 g, 0.39 mmol, 1.0 eq.), 1-(4-fluoro-phenylcarbamoyl)-cyclopropanecarboxylic acid (0.133 g, 0.59 mmol, 1.5 eq), HATU (0.379 g, 0.98 mmol, 2.5 eq), TEA (0.17 ml, 1.17 mmol, 3 eq), and dry DMF (5 ml). The mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with ethyl acetate and washed with (2×) H2O (50 ml), sat'd NaHCO3 (2×), 5% LiCl (3×), sat'd NaCl (1×), dried (Na2SO4), and concentrated in vacuo, giving 4-(2-fluoro-4-{[1-(4-fluoro-phenylcarbamoyl)-cyclopropanecarbonyl]-amino}-phenoxy)-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid ethyl ester as a cream solid (0.138 g, 53% yield). MS (ESI) for C32H35F2N5O6Si: 517 (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-3b7b8320dcc04cf0bde05745492b49e8
Source dataset
uspto-grants-2011_07
Patent number
US07977345B2

Reaction notes

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