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 1631484Notes

Reaction equation

HRID 1631484 reaction equation
C[O:2][C:3](=[O:31])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH2:24][CH3:25])(=[O:23])=[O:22])=[CH:17][C:16]=2[C:26]([F:29])([F:28])[F:27])[C:6]=1[CH3:30].COC(=O)CC1C2C(=NC=CC=2)NC=1C.CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.BrCC1C=CC(S(CC)(=O)=O)=CC=1C(F)(F)F>CN(C=O)C>[CH2:24]([S:21]([C:18]1[CH:19]=[CH:20][C:15]([CH2:14][N:7]2[C:8]3=[N:9][CH:10]=[CH:11][CH:12]=[C:13]3[C:5]([CH2:4][C:3]([OH:31])=[O:2])=[C:6]2[CH3:30])=[C:16]([C:26]([F:28])([F:29])[F:27])[CH:17]=1)(=[O:23])=[O:22])[CH3:25]

Participants

6

Reactant 4

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 67219276[1-(4-Ethanesulfonyl-2-trifluoromethyl-benzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid methyl esterHCID 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

[1-(4-Ethanesulfonyl-2-trifluoromethyl-benzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid methyl ester: 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-ab4b18a44e3a4aa2aa696cb2aab3fcb0
Source dataset
uspto-grants-2014_07
Patent number
US08791256B2

Reaction notes

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