Hydrochloric Acid → 3-[1-(2-Aminoethyl)-1,2,3,6-tetrahydropyridin-4-yl]-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-furo[3,2-c]pyridin-6-ylamine

HRID 911961Notes

Reaction equation

HRID 911961 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[C@H:10]([O:12][C:13]1[C:14]2[O:22][CH:21]=[C:20]([C:23]3[CH2:24][CH2:25][NH:26][CH2:27][CH:28]=3)[C:15]=2[CH:16]=[N:17][C:18]=1[NH2:19])[CH3:11].O=[CH:30][CH2:31][NH:32]C(=O)OC(C)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(Cl)Cl.Cl.O1CCOCC1.CCOCC>>[NH2:32][CH2:31][CH2:30][N:26]1[CH2:25][CH:24]=[C:23]([C:20]2[C:15]3[CH:16]=[N:17][C:18]([NH2:19])=[C:13]([O:12][C@@H:10]([C:3]4[C:4]([Cl:9])=[CH:5][CH:6]=[C:7]([F:8])[C:2]=4[Cl:1])[CH3:11])[C:14]=3[O:22][CH:21]=2)[CH2:28][CH2:27]1

Participants

8

Reactant 7

HCID 313Hydrochloric Acid2×HCID 3283Diethyl EtherHCID 6344DichloromethaneHCID 312751,4-DioxaneHCID 4247255tert-butyl N-(2-oxoethyl)carbamateHCID 5049666Sodium triacetoxyborohydrideHCID 578124807-[(R)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-3-(1,2,3,6-tetrahydropyridin-4-yl)furo[3,2-c]pyridin-6-ylamine

Product 1

HCID 441815383-[1-(2-Aminoethyl)-1,2,3,6-tetrahydropyridin-4-yl]-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-furo[3,2-c]pyridin-6-ylamine

Procedure

A mixture of 7-[(R)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-3-(1,2,3,6-tetrahydropyridin-4-yl)-furo[3,2-c]pyridin-6-ylamine (35.0 mg, 0.0829 mmol), tert-butyl N-(2-oxoethyl)carbamate (26.4 mg, 0.166 mmol), sodium triacetoxyborohydride (19.3 mg, 0.0912 mmol) and DCM (3 mL, 50 mmol) was stirred at rt for 30 min. The solution was transferred to a separatory funnel and extracted with DCM and sat. NaHCO3. The organic layer was concentrated in vacuo, redissolved in 1,4-dioxane and transferred to a sealed tube. 4 M of HCl in 1,4-Dioxane (0.5 mL, 2 mmol) was added, and the mixture was heated to 50° C. for 2 h. The solution was concentrated in vacuo, redissolved in DCM and transferred to a separatory funnel. The organic layer was washed with sat. NaHCO3, concentrated in vacuo, and loaded onto a prep TLC plate, eluting with 7% (7N NH3 in MeOH)/DCM. The band containing the pure product was filtered off using 1:1 MeOH/DCM. To the filtrate was added 2.0 M of HCl in Et2O (0.207 mL, 0.414 mmol) to form the HCl salt, and the mixture was stirred for 30 min at rt. The material was concentrated in vacuo to afford the title compound as bis-HCl salt. 1H NMR (CD3OD, 400 MHz): δ=1.88 (d, J=6.8 Hz, 3H), 2.56 (d, J=1.5 Hz, 2H), 2.79 (ddd, J=19.3, 5.8, 5.7 Hz, 4H), 3.12 (t, J=5.9 Hz, 2H), 3.28 (d, J=2.5 Hz, 2H), 6.27 (br, s, 1H), 6.50 (q, J=6.8 Hz, 1H), 7.22 (t, J=8.6 Hz, 1H), 7.40 (dd, J=9.0, 4.9 Hz, 1H), 7.63 (s, 1H), 8.17 (s, 1H). MS (ES+): m/z 465.04 [MH+]. HPLC: tR=2.43 min (ZQ3, polar—5 min).

Workup

  1. customThe solution was transferred to a separatory funnel
  2. extractionextracted with DCM and sat. NaHCO3
  3. concentrationThe organic layer was concentrated in vacuo
  4. dissolutionredissolved in 1,4-dioxane
  5. customtransferred to a sealed tube
  6. temperaturethe mixture was heated to 50° C. for 2 h
  7. concentrationThe solution was concentrated in vacuo
  8. dissolutionredissolved in DCM
  9. customtransferred to a separatory funnel
  10. washThe organic layer was washed with sat. NaHCO3
  11. concentrationconcentrated in vacuo
  12. washeluting with 7% (7N NH3 in MeOH)/DCM
  13. additionThe band containing the pure product
  14. filtrationwas filtered off

Sources & evidence

ORD record
ord-4ccc76bda2ce40a9bc9e94b754552319
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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