1-Hydroxybenzotriazole → 2-((R)-3-(3,5-difluorophenyl)-1-methyl-5-oxo-8,11-dioxa-1,4-diazaspiro[5.6]dodecan-4-yl)-N-((R)-2'-oxo-1,1',2',3-tetrahydrospiro[inden-2,3'-pyrrolo[2,3-b]pyridin]-5-yl)acetamide

HRID 1615780Notes

Reaction equation

HRID 1615780 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[N:14]([CH2:15][C:16](O)=[O:17])[C:13](=[O:19])[C:12]3([CH2:25][O:24][CH2:23][CH2:22][O:21][CH2:20]3)[N:11]([CH3:26])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[NH2:27][C:28]1[CH:29]=[C:30]2[C:43](=[CH:44][CH:45]=1)[CH2:42][C@:32]1([C:40]3[C:35](=[N:36][CH:37]=[CH:38][CH:39]=3)[NH:34][C:33]1=[O:41])[CH2:31]2.Cl.C(N=C=NCCCN(C)C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[N:14]([CH2:15][C:16]([NH:27][C:28]3[CH:29]=[C:30]4[C:43](=[CH:44][CH:45]=3)[CH2:42][C@:32]3([C:40]5[C:35](=[N:36][CH:37]=[CH:38][CH:39]=5)[NH:34][C:33]3=[O:41])[CH2:31]4)=[O:17])[C:13](=[O:19])[C:12]3([CH2:25][O:24][CH2:23][CH2:22][O:21][CH2:20]3)[N:11]([CH3:26])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 53260812(R)-5-Amino-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-oneHCID 68763645(R)-2-(3-(3,5-difluorophenyl)-1-methyl-5-oxo-8,11-dioxa-1,4-diazaspiro[5.6]dodecan-4-yl)-ethanoic acid

Product 1

HCID 498426072-((R)-3-(3,5-difluorophenyl)-1-methyl-5-oxo-8,11-dioxa-1,4-diazaspiro[5.6]dodecan-4-yl)-N-((R)-2'-oxo-1,1',2',3-tetrahydrospiro[inden-2,3'-pyrrolo[2,3-b]pyridin]-5-yl)acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

75 mg (0.20 mmol) (R)-2-(3-(3,5-difluorophenyl)-1-methyl-5-oxo-8,11-dioxa-1,4-diazaspiro[5.6]dodecan-4-yl)-ethanoic acid, 55 mg (0.22 mmol) (R)-5-amino-1,3-dihydrospiro[inden-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one, 50 mg (0.26 mmol) 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-hydrochloride, 35 mg (0.26 mmol) HOBT, 0.07 ml (0.50 mmol) TEA and 1.5 ml DMF were stirred overnight at RT. The reaction mixture was concentrated by rotary evaporation. The residue was stirred with 15 ml of a 1.25M methanolic hydrochloric acid for 1 h at 50° C. The mixture was concentrated by rotary evaporation and the residue was purified by HPLC. The fractions containing the product were combined and lyophilised.

Workup

  1. concentrationThe reaction mixture was concentrated by rotary evaporation
  2. concentrationThe mixture was concentrated by rotary evaporation
  3. customthe residue was purified by HPLC
  4. additionThe fractions containing the product

Sources & evidence

ORD record
ord-8da1f394775c447fba1677e818c9e9da
Source dataset
uspto-grants-2014_07
Patent number
US08765763B2

Reaction notes

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