Hydrochloric Acid → HCID 66823780, compound

HRID 1910038Notes

Reaction equation

HRID 1910038 reaction equation
[C:1]([C:3]1[C:4]2[O:26][CH:25]=[C:24]([C:27]3[CH:28]=[C:29]4[C:33](=[CH:34][CH:35]=3)[N:32]([C:36](=[O:46])[CH2:37][C:38]3[CH:43]=[C:42]([F:44])[CH:41]=[CH:40][C:39]=3[F:45])[CH2:31][CH2:30]4)[C:5]=2[C:6]([N:9](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=[N:7][CH:8]=1)#[N:2].Cl.O1CCOCC1>>[NH2:9][C:6]1[C:5]2[C:24]([C:27]3[CH:28]=[C:29]4[C:33](=[CH:34][CH:35]=3)[N:32]([C:36](=[O:46])[CH2:37][C:38]3[CH:43]=[C:42]([F:44])[CH:41]=[CH:40][C:39]=3[F:45])[CH2:31][CH2:30]4)=[CH:25][O:26][C:4]=2[C:3]([C:1]#[N:2])=[CH:8][N:7]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 66823739HCID 66823739, compound

Product 1

HCID 66823780HCID 66823780, compoundYield 48.2%

Procedure

A mixture of bis(1,1-dimethylethyl) (7-cyano-3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}furo[3,2-c]pyridin-4-yl)imidodicarbonate (359 mg, 3:2 mixture with non-Boc as described above) and 4.0 M HCl in dioxane (3.0 mL, 12.00 mmol) was stirred at room temperature under Nitrogen for 14 hr. The mixture was concentrated in vacuo and taken up in EtOAc (50 mL) and saturated aqueous sodium bicarbonate (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (50 mL). The combined organic layers were washed with brine (1×50 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (Analogix, 40 g SiO2, 15%-85% EtOAc in hexanes gradient over 52 minutes) to give 4-amino-3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}furo[3,2-c]pyridine-7-carbonitrile (118 mg, 45.7% yield) as a white solid. LC/MS (ES) m/z=431 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 3.28 (t, 2H), 3.97 (s, 2H), 4.30 (t, J=8.46 Hz, 2H), 6.57 (br. s., 2H), 7.14-7.33 (m, 4H), 7.40 (s, 1H), 8.09-8.17 (m, 2H), 8.38 (s, 1H).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (50 mL)
  4. washThe combined organic layers were washed with brine (1×50 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (Analogix, 40 g SiO2, 15%-85% EtOAc in hexanes gradient over 52 minutes)

Sources & evidence

ORD record
ord-947c0a7dd10a4744b4da221ac7db08ee
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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