Water → HCID 59641770, compound

HRID 2250878Notes

Reaction equation

HRID 2250878 reaction equation
[C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([N:13]([CH:24]3[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)[C:14](=[O:23])/[CH:15]=[CH:16]/[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].Br[CH:37]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:38]([O:40][CH3:41])=[O:39].O>CN(C=O)C.C(Cl)Cl>[CH3:41][O:40][C:38](=[O:39])[CH:37]([N:27]1[CH2:28][CH2:29][CH:24]([N:13]([C:10]2[CH:11]=[C:12]3[C:7]([CH2:6][CH2:5][N:4]3[C:1](=[O:3])[CH3:2])=[CH:8][CH:9]=2)[C:14](=[O:23])/[CH:15]=[CH:16]/[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:25][CH2:26]1)[C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 137806Benzeneacetic acid, alpha-bromo-, methyl esterHCID 59641765HCID 59641765, compound

Product 1

HCID 59641770HCID 59641770, compoundYield 84.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of trans-N-(1-acetyl-2,3-dihydro-1H-indol-6-yl)-3-phenyl-N-piperidin-4-yl-acrylamide (Example 41, Step C; 49 mg, 0.13 mmol) in DMF (0.5 mL) and DCM (2 mL) was added Na2CO3 (41 mg, 0.39 mmol) followed by methyl α-bromophenylacetate (26 μL, 0.16 mmol). After stirring overnight, the reaction mixture was poured into H2O and DCM was added. The organic fraction was washed with brine (3×), dried (Na2SO4), and concentrated. Purification by silica gel chromatography (2% methanol (2 M NH3) in DCM) afforded 59 mg (84%) of the title compound. 1H NMR (400 MHz, CDCl3): 8.04 (br d, J=12.4 Hz, 1H), 7.62 (d, J=15.4 Hz, 1H), 7.38-7.22 (m, 10H), 7.18 (dd, J=8.8, 8.0 Hz, 1H), 6.73 (dd, J=17.2, 7.8 Hz, 1H), 6.15 (d, J=15.6 Hz, 1H), 4.74 (br dd, J=12.4, 12.1 Hz, 1H), 4.17 (dd, J=8.8, 8.3 Hz, 2H), 3.94 (d, J=3.8 Hz, 1H), 3.65 (s, 3H), 3.31-3.24 (m, 2H), 3.01-2.94 (m, 1H), 2.76-2.69 (m, 1H), 2.34-2.22 (m, 1H), 2.24 (d, J=5.3 Hz, 3H), 2.02-1.76 (m, 2H), 1.76-1.63 (m, 1H), 1.61 (s, 3H), 1.58-1.40 (m, 1H). MS: exact mass calculated for C33H35N3O4, 537.3; m/z found, 538.5 [M+H]+.

Workup

  1. additionwas added
  2. washThe organic fraction was washed with brine (3×)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography (2% methanol (2 M NH3) in DCM)

Sources & evidence

ORD record
ord-f495a1fd1cb24a9db38b58bfc8ae7830
Source dataset
uspto-grants-2008_01
Patent number
US07317025B2

Reaction notes

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