Hydrochloric Acid → HCID 86653010, compound

HRID 1971212Notes

Reaction equation

HRID 1971212 reaction equation
[C:1]12([C:9]3[CH:10]=[C:11]([N:19]4[C:23]([NH2:24])=[N:22][C:21]([NH:25][C:26]5[CH:27]=[CH:28][C:29]6[CH2:35][CH2:34][C@H:33]([NH:36]C(OC(C)(C)C)=O)[CH2:32][CH2:31][C:30]=6[CH:44]=5)=[N:20]4)[N:12]=[C:13]4[C:18]=3[NH:17][CH2:16][CH2:15][CH2:14]4)[CH2:8][CH2:7][C:4]([CH:5]=[CH:6]1)=[CH:3][CH2:2]2.Cl.CO.[OH-].[Na+]>O1CCOCC1>[C:1]12([C:9]3[CH:10]=[C:11]([N:19]4[C:23]([NH2:24])=[N:22][C:21]([NH:25][C:26]5[CH:27]=[CH:28][C:29]6[CH2:35][CH2:34][C@H:33]([NH2:36])[CH2:32][CH2:31][C:30]=6[CH:44]=5)=[N:20]4)[N:12]=[C:13]4[C:18]=3[NH:17][CH2:16][CH2:15][CH2:14]4)[CH2:8][CH2:7][C:4]([CH:3]=[CH:2]1)=[CH:5][CH2:6]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 86653011HCID 86653011, compound

Product 1

HCID 86653010HCID 86653010, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

(7S)-1-(1,4-ethano-8-phenyl-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N3-(7-(t-butoxycarbonylamino)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5-diamine (23 mg, 0.038 mmol) was added to a 4M solution of HCl in dioxane. In order to improve solubility, 2 mL of MeOH were added which resulted in a clear solution. The reaction mixture was stirred for 6 h at ambient temperature and then neutralized with 2M NaOH which caused the precipitation of the free amine. The product was filtered off, washed with water and dried over night in HV to yield the amino compound, (7S)-1-(1,4-ethano-8-phenyl-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N3-(7-amino-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5-diamine (18 mg, 96%). The product was then dissolved in dry DCM. Subsequently, acetaldehyde (˜5 mg, 0.1 mmol) and NaBH(OAc)3 (21 mg, 0.1 mmol) were added. After the mixture was stirred for 2 d at ambient temperature, the solvents were evaporated and the desired product, (7S)-1-(1,4-ethano-8-phenyl-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N3-(7-(diethylamino)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5-diamine, compound #35, was isolated via reverse phase HPLC (10.8 mg, 52% two steps); 1H NMR (DMSO-d6, 300 MHz): 9.04 (s, 1H), 8.69 (s br, 1H), 7.75 (s br, 2H), 7.54-7.66 (m, 5H), 7.41 (d, 1H), 7.26 (s, 1H), 7.01 (d, 1H), 2.87-3.18 (m, 8H), 2.60-2.81 (m, 4H), 2.51-2.55 (m, 2H), 2.00-2.28 (m, 4H), 1.66-1.87 (m, 2H), 1.30-1.56 (m, 2H), 1.12-1.28 (m, 6H) ppm; MS (ES) 549.22 (M+H).

Workup

  1. additionwere added which
  2. customresulted in a clear solution
  3. customthe precipitation of the free amine
  4. filtrationThe product was filtered off
  5. washwashed with water
  6. customdried over night in HV

Sources & evidence

ORD record
ord-06222356708a452d838d07cccb67ef68
Source dataset
uspto-grants-2013_04
Patent number
US08431594B2

Reaction notes

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