Nitric Acid → (S)-5-Amino-6-nitro-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

HRID 2262837Notes

Reaction equation

HRID 2262837 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:25](=[CH:26][CH:27]=1)[CH2:24][C@:6]1([C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[N:8](COCC[Si](C)(C)C)[C:7]1=[O:23])[CH2:5]2.FC(F)(F)C(OC(=O)C(F)(F)F)=O.NC1C=CC=CC=1.FC(F)(F)C(NC1C=CC=CC=1)=O.[N+:61]([O-])([OH:63])=[O:62].FC(F)(F)C(O)=O.C(N)CN>C(Cl)Cl.O>[NH2:1][C:2]1[CH:3]=[C:4]2[C:25](=[CH:26][C:27]=1[N+:61]([O-:63])=[O:62])[CH2:24][C@:6]1([C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]1=[O:23])[CH2:5]2

Participants

10

Reactant 7

HCID 944Nitric AcidHCID 3301EthylenediamineHCID 6115AnilineHCID 6422Trifluoroacetic acidHCID 9845Trifluoroacetic anhydrideHCID 678812,2,2-Trifluoro-N-phenylacetamideHCID 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 67174155(S)-5-Amino-6-nitro-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of (R)-5-amino-1′-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (28.7 g, 75.2 mmol, described in Intermediate 3) in CH2Cl2 (100 mL) was added trifluoroacetic anhydride (106 mL, 752 mmol). The mixture was stirred for 10 min, after which time the aniline had been converted to the corresponding trifluoroacetanilide. The resulting mixture was cooled in an ice-salt bath and 15.8 M nitric acid (5.0 mL, 79 mmol) was added dropwise over 15 min, keeping the reaction temperature at 10-12° C. After the addition, the reaction mixture was stirred for 30 min, then H2O (12 mL) was carefully added, followed by trifluoroacetic acid (100 mL) and CH2Cl2 (100 mL). The mixture was allowed to warm to ambient temperature and stirring was continued for 2 h, followed by concentration to dryness in vacuo. The residue was dissolved in MeOH (200 mL) and the solution was adjusted to pH 10 by addition of 10 N NaOH. Ethylene diamine (5 mL, 75 mmol) was added and the mixture was stirred at ambient temperature for 18 h, then diluted with H2O (200 mL). The resulting solid was isolated by filtration, washed with H2O, and dried in vacuo to give the title compound. MS: m/z=297 (M+1).

Workup

  1. temperatureThe resulting mixture was cooled in an ice-salt bath
  2. customat 10-12° C
  3. additionAfter the addition
  4. stirringthe reaction mixture was stirred for 30 min
  5. stirringstirring
  6. waitwas continued for 2 h
  7. concentrationfollowed by concentration to dryness in vacuo
  8. dissolutionThe residue was dissolved in MeOH (200 mL)
  9. additionthe solution was adjusted to pH 10 by addition of 10 N NaOH
  10. stirringthe mixture was stirred at ambient temperature for 18 h
  11. customThe resulting solid was isolated by filtration
  12. washwashed with H2O
  13. customdried in vacuo

Sources & evidence

ORD record
ord-77db0527e30346708c4e7cbc89b988db
Source dataset
uspto-grants-2010_12
Patent number
US07851464B2

Reaction notes

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