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

HRID 1254881Notes

Reaction equation

HRID 1254881 reaction equation
C[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]([CH2:45][CH3:46])(=[O:44])=[O:43])=[CH:38][C:37]=1[C:47]([F:50])([F:49])[F:48]>CN(C=O)C>[CH2:45]([S:42]([C:39]1[CH:40]=[CH:41][C:36]([CH2:35][N:7]2[C:8]3=[N:9][CH:10]=[CH:11][CH:12]=[C:13]3[C:5]([CH2:4][C:3]([OH:2])=[O:15])=[C:6]2[CH3:14])=[C:37]([C:47]([F:49])([F:48])[F:50])[CH:38]=1)(=[O:43])=[O:44])[CH3:46]

Participants

5

Reactant 3

HCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 67218699methyl 2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)acetateHCID 672198351-Bromomethyl-4-ethanesulfonyl-2-trifluoromethyl-benzene

Product 1

HCID 11683632[1-(4-Ethanesulfonyl-2-trifluoromethyl-benzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-acetic acid methyl ester (0.77 g, 3.78 mmol) in dry DMF (12 ml) under an inert atmosphere of Argon is added dropwise, BEMP (1.75 ml, 6.04 mmol). The mixture was allowed to stir at room temperature for 1 hour and then treated with 1-bromomethyl-4-ethanesulfonyl-2-trifluoromethyl-benzene (2 g, 6.04 mmol). Stirring continues for a further 2 hours after which time, the reaction mixture is partitioned between ethyl acetate/diethyl ether (80 ml of a 1:1 mixture) and water (100 ml). The organic portion is separated and washed with brine and concentrated in vacuo. Purification of the crude by chromatography on silica eluting with iso-hexane/ethyl acetate (3:1 increasing to 2:1) yields the titled product. (MH+ 455)

Workup

  1. stirringStirring
  2. waitcontinues for a further 2 hours
  3. customafter which time, the reaction mixture is partitioned between ethyl acetate/diethyl ether (80 ml of a 1:1 mixture) and water (100 ml)
  4. customThe organic portion is separated
  5. washwashed with brine
  6. concentrationconcentrated in vacuo
  7. customPurification of the crude by chromatography on silica eluting with iso-hexane/ethyl acetate (3:1 increasing to 2:1)

Sources & evidence

ORD record
ord-e5ca365717bf41689f747e5f083a4cef
Source dataset
uspto-grants-2013_06
Patent number
US08455645B2

Reaction notes

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