Ammonia → [(S)-2-(7-Carbamoyl-furo[2,3-g]indazol-1-yl)-1-methylethyl]-carbamic acid benzyl ester

HRID 1453895Notes

Reaction equation

HRID 1453895 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH3:29])[CH2:13][N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]3[O:25][C:24]([C:26](O)=[O:27])=[CH:23][C:21]3=2)[CH:16]=[N:15]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.O[N:32]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.N.O1CCOCC1.[Cl-].[NH4+]>CN(C=O)C>[CH2:1]([O:8][C:9](=[O:10])[NH:11][C@@H:12]([CH3:29])[CH2:13][N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]3[O:25][C:24]([C:26](=[O:27])[NH2:32])=[CH:23][C:21]3=2)[CH:16]=[N:15]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 6

HCID 222AmmoniaHCID 25517Ammonium ChlorideHCID 312751,4-DioxaneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 688554451-((S)-2-Benzyloxycarbonylaminopropyl)-1H-furo[2,3-g]indazole-7-carboxylic acid

Product 1

HCID 68854663[(S)-2-(7-Carbamoyl-furo[2,3-g]indazol-1-yl)-1-methylethyl]-carbamic acid benzyl esterYield 169.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of the product from Step A (0.17 g, 0.43 mmol) in DMF (5 mL) was added 1-hydroxy-benzotriazole hydrate (0.029 g, 0.21 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.13 g, 0.65 mmol) followed by a solution of ammonia in dioxane (0.5 M, 1.72 mL, 0.86 mmol). After 18 h, a saturated aqueous solution of ammonium chloride (20 mL) added and the mixture was extracted with ethyl acetate (3×50 mL). The combined extracts were washed with brine, dried and evaporated. The residue was purified by chromatography (silica, dichloromethane, 5% methanol in dichloromethane) to give an oil (0.14 g, 83%): MS (ES) m/z 393 (M+); 1H NMR (CDCl3) δ 8.20 (brs, 1H), 8.04 (s, 1H), 8.01 (s, 1H), 7.69 (d, 1H, J=8.0 Hz), 7.32-7.23 (m, 6H), 6.76 (brs, 2H), 5.03 (m, 2H), 4.63 (m, 2H), 4.40 (m, 1H), 1.16 (d, 3H, J=8.0 Hz).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
  2. washThe combined extracts were washed with brine
  3. customdried
  4. customevaporated
  5. customThe residue was purified by chromatography (silica, dichloromethane, 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-70e422b1f0ca4396964788ca247ed484
Source dataset
uspto-grants-2009_01
Patent number
US07476687B2

Reaction notes

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