1,2-Dichloroethane → 2-[(6S)-6-(3,5-Difluorophenyl)-3,3-dimethyl-2-oxopiperidin-1-yl]-N-((2R)-2'-oxo-1'-{[2-(trimethylsilyl)ethoxy]methyl}-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide

HRID 1866729Notes

Reaction equation

HRID 1866729 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[N:14]([CH2:15][C:16]([OH:18])=O)[C:13](=[O:19])[C:12]([CH3:21])([CH3:20])[CH2:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[NH2:22][C:23]1[CH:24]=[C:25]2[C:46](=[CH:47][CH:48]=1)[CH2:45][C@:27]1([C:35]3[C:30](=[N:31][CH:32]=[CH:33][CH:34]=3)[N:29]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[C:28]1=[O:44])[CH2:26]2.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[N:14]([CH2:15][C:16]([NH:22][C:23]3[CH:24]=[C:25]4[C:46](=[CH:47][CH:48]=3)[CH2:45][C@:27]3([C:35]5[C:30](=[N:31][CH:32]=[CH:33][CH:34]=5)[N:29]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:41])([CH3:42])[CH3:43])[C:28]3=[O:44])[CH2:26]4)=[O:18])[C:13](=[O:19])[C:12]([CH3:21])([CH3:20])[CH2:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 66973553[(6S)-6-(3,5-difluorophenyl)-3,3-dimethyl-2-oxopiperidin-1-yl]acetic acid2×HCID 66973634(R)-5-amino-1'-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one2×

Product 1

HCID 669731272-[(6S)-6-(3,5-Difluorophenyl)-3,3-dimethyl-2-oxopiperidin-1-yl]-N-((2R)-2'-oxo-1'-{[2-(trimethylsilyl)ethoxy]methyl}-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of [(6S)-6-(3,5-difluorophenyl)-3,3-dimethyl-2-oxopiperidin-1-yl]acetic acid (21 mg, 0.07 mmol, described in Intermediate 49), (R)-5-amino-1′-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (26 mg, 0.07 mmol, described in Intermediate 9, step B), HOBT (15 mg, 0.10 mmol), and EDC (19 mg, 0.10 mmol) in DMF (0.5 mL) was stirred at ambient temperature for 18 h. The reaction mixture was partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (20 mL). The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound. MS: m/z=661 (M+1).

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (20 mL)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5875226e47bd4a38a3eff3836ea6f58b
Source dataset
uspto-grants-2009_12
Patent number
US07629338B2

Reaction notes

Loading…