2-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amine → methyl 2-(2-methyl-1-(4-(methylsulfonyl)-2-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acetate

HRID 1260644Notes

Reaction equation

HRID 1260644 reaction equation
[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[NH:7][C:6]=1[CH3:14].CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.Br[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([S:42]([CH3:45])(=[O:44])=[O:43])=[CH:38][C:37]=1[C:46]([F:49])([F:48])[F:47]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH2:35][C:36]2[CH:41]=[CH:40][C:39]([S:42]([CH3:45])(=[O:44])=[O:43])=[CH:38][C:37]=2[C:46]([F:48])([F:47])[F:49])[C:6]=1[CH3:14]

Participants

5

Reactant 3

HCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 513420492-(Bromomethyl)-5-(methylsulphonyl)benzotrifluorideHCID 67218699methyl 2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)acetate

Product 1

HCID 67219460methyl 2-(2-methyl-1-(4-(methylsulfonyl)-2-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

To an ice-cooled solution of (2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-acetic acid methyl ester ((12.8 g, 62.8 mmol) in dry DMF (400 ml) under an inert atmosphere of Argon is added dropwise, BEMP (18.1 ml, 62.8 mmol) over two minutes. After stirring at 10° C. for 40 minutes, the resulting solution is treated dropwise with 1-bromomethyl-4-methanesulfonyl-2-trifluoromethyl-benzene (23.8 g, 75.4 mmol) and allowed to warm to room temperature while stirring overnight. The reaction is concentrated in vacuo with toluene azeotroping and the resulting oil is partitioned between water (400 ml) and DCM (500 ml) and extracted with DCM (500 ml). The organic portions are combined and washed with water (2×200 ml). The resulting suspension is filtered and concentrated in vacuo with toluene azeotroping. The crude is purified by chromatography on silica eluting with iso-hexane/acetone (16:4) to yield the titled product. (MH+ 441)

Workup

  1. additionis added dropwise
  2. temperatureto warm to room temperature
  3. stirringwhile stirring overnight
  4. concentrationThe reaction is concentrated in vacuo with toluene azeotroping
  5. customthe resulting oil is partitioned between water (400 ml) and DCM (500 ml)
  6. extractionextracted with DCM (500 ml)
  7. washwashed with water (2×200 ml)
  8. filtrationThe resulting suspension is filtered
  9. concentrationconcentrated in vacuo with toluene azeotroping
  10. customThe crude is purified by chromatography on silica eluting with iso-hexane/acetone (16:4)

Sources & evidence

ORD record
ord-93c7944aaf8545939bc01c8f1cc1c412
Source dataset
uspto-grants-2013_06
Patent number
US08470848B2

Reaction notes

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