Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → 3-[1-[3,5-Dimethyl-4-(4-morpholin-4-yl-piperidine-1-carbonyl)-1H-pyrrol-2-yl]-meth-(Z)-ylidene]4-(3-fluoro-phenyl)-1,3-dihydro-indol-2-one

HRID 1839818Notes

Reaction equation

HRID 1839818 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2/[C:10](=[CH:18]/[C:19]2[NH:23][C:22]([CH3:24])=[C:21]([C:25]([OH:27])=O)[C:20]=2[CH3:28])/[C:11](=[O:17])[NH:12]3)[CH:5]=[CH:6][CH:7]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH:56]1[CH2:61][CH2:60][CH:59]([N:62]2[CH2:67][CH2:66][O:65][CH2:64][CH2:63]2)[CH2:58][CH2:57]1.[Li+].[Cl-]>CN(C=O)C.C(Cl)(Cl)Cl.C(O)(C)C>[CH3:28][C:20]1[C:21]([C:25]([N:56]2[CH2:61][CH2:60][CH:59]([N:62]3[CH2:67][CH2:66][O:65][CH2:64][CH2:63]3)[CH2:58][CH2:57]2)=[O:27])=[C:22]([CH3:24])[NH:23][C:19]=1/[CH:18]=[C:10]1\[C:11](=[O:17])[NH:12][C:13]2[C:9]\1=[C:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=1)[CH:16]=[CH:15][CH:14]=2

Participants

7

Reactant 4

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 433294Lithium ChlorideHCID 7957244-MorpholinopiperidineHCID 697413865-[4-(3-Fluoro-phenyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid

Product 1

HCID 600615833-[1-[3,5-Dimethyl-4-(4-morpholin-4-yl-piperidine-1-carbonyl)-1H-pyrrol-2-yl]-meth-(Z)-ylidene]4-(3-fluoro-phenyl)-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21906603Chloroform isopropyl alcoholSolvent

Procedure

5-[4-(3-Fluoro-phenyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (1 eq.) and BOP (1.25 eq.) were suspended in DMF (5 mL) at rt and TEA (2.4 eq.) was added. After 15 mina, to the homogenous reaction mixture was added 4-piperidin-4-yl-morpholine (1.25 eq.) all at once. After stirring for 2 days, the reaction was added to a mixture of chloroform-isopropanol (5:1) and 5% aq. LiCl. The organic layer was separated, washed with 5% aq. LiCl (2×), 1M aq. NaOH (3×), brine, dried and concentrated. The residue was purified to give the titled compound.

Workup

  1. customThe organic layer was separated
  2. washwashed with 5% aq. LiCl (2×), 1M aq. NaOH (3×), brine
  3. customdried
  4. concentrationconcentrated
  5. customThe residue was purified

Sources & evidence

ORD record
ord-886e18696d914dc7b2703e3f97beba43
Source dataset
uspto-grants-2004_01
Patent number
US06677368B2

Reaction notes

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