Trifluoroacetic acid → HCID 53466953, compound

HRID 1909940Notes

Reaction equation

HRID 1909940 reaction equation
[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:12]=[C:13]4[C:17](=[CH:18][CH:19]=3)[N:16]([C:20](=[O:28])[CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:15][CH2:14]4)=[CH:9][S:10][C:6]=2[C:5]([C:29]2[CH2:30][CH2:31][N:32](C(OC(C)(C)C)=O)[CH2:33][CH:34]=2)=[CH:4][N:3]=1.C(O)(C(F)(F)F)=O>ClCCl>[C:22]1([CH2:21][C:20]([N:16]2[C:17]3[C:13](=[CH:12][C:11]([C:8]4[C:7]5[C:2]([NH2:1])=[N:3][CH:4]=[C:5]([C:29]6[CH2:30][CH2:31][NH:32][CH2:33][CH:34]=6)[C:6]=5[S:10][CH:9]=4)=[CH:19][CH:18]=3)[CH2:14][CH2:15]2)=[O:28])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66823627HCID 66823627, compound

Product 1

HCID 53466953HCID 53466953, compoundYield 67.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 1,1-dimethylethyl 4-{4-amino-3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]thieno[3,2-c]pyridin-7-yl}-3,6-dihydro-1(2H)-pyridinecarboxylate (54 mg, 0.095 mmol) and TFA (1.0 mL, 12.98 mmol) in Dichloromethane (DCM) (1 mL) was stirred at room temperature under Nitrogen for 1 hr. The mixture was then concentrated in vacuo, NaHCO3 (5 mL) was added, and it was extracted with methylene chloride (3×5 mL). The extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (Analogix, 12 g SiO2, DCM to 90/10/1 DCM/MeOH/NH4OH gradient over 20 minutes) to give 3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]-7-(1,2,3,6-tetrahydro-4-pyridinyl)thieno[3,2-c]pyridin-4-amine (33 mg, 0.064 mmol, 66.8% yield) as a beige solid. LC/MS (ES) m/z=467 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 2.42 (d, J=1.77 Hz, 2H), 2.96 (t, J=5.56 Hz, 2H), 3.23 (t, J=8.34 Hz, 2H), 3.43 (d, J=3.03 Hz, 2H), 3.89 (s, 2H), 4.25 (t, J=8.46 Hz, 2H), 5.40 (br. s., 2H), 6.16 (br. s., 1H), 7.19-7.39 (m, 7H), 7.43 (s, 1H), 7.79 (s, 1H), 8.16 (d, J=8.34 Hz, 1H).

Workup

  1. concentrationThe mixture was then concentrated in vacuo, NaHCO3 (5 mL)
  2. additionwas added
  3. extractionit was extracted with methylene chloride (3×5 mL)
  4. dry with materialThe extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (Analogix, 12 g SiO2, DCM to 90/10/1 DCM/MeOH/NH4OH gradient over 20 minutes)

Sources & evidence

ORD record
ord-2f1aaea402a842bcaef453dce2e52fa5
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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