Trifluoroacetic acid → HCID 53467174, compound

HRID 1909950Notes

Reaction equation

HRID 1909950 reaction equation
C(O)(C(F)(F)F)=O.[NH2:8][C:9]1[C:14]2[C:15]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[N:23]([C:27](=[O:35])[CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:22][CH2:21]4)=[CH:16][S:17][C:13]=2[C:12]([CH:36]2[CH2:41][CH2:40][N:39](C(OC(C)(C)C)=O)[CH2:38][CH2:37]2)=[CH:11][N:10]=1>ClCCl>[C:29]1([CH2:28][C:27]([N:23]2[C:24]3[C:20](=[CH:19][C:18]([C:15]4[C:14]5[C:9]([NH2:8])=[N:10][CH:11]=[C:12]([CH:36]6[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]6)[C:13]=5[S:17][CH:16]=4)=[CH:26][CH:25]=3)[CH2:21][CH2:22]2)=[O:35])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66823764HCID 66823764, compound

Product 1

HCID 53467174HCID 53467174, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (0.5 mL, 6.49 mmol) was added to a suspension of 1,1-dimethylethyl 4-{4-amino-3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]thieno[3,2-c]pyridin-7-yl}-1-piperidinecarboxylate (90 mg, 0.158 mmol) in Dichloromethane (DCM) (3.5 mL), and the mixture was stirred at room temperature under Nitrogen for 30 min. The reaction mixture was then concentrated in vacuo, taken up in DCM, and passed through a PL-HCO3 MP-resin cartridge, rinsing with more DCM. The filtrate was concentrated in vacuo. The solid (labeled 96-A1) was not quite pure enough for submission (impurities best visible by NMR), so the residue was purified by flash chromatography (Analogix, 24 g SiO2, DCM to 80/20/2 DCM/MeOH/NH4OH gradient over 30 minutes) to give 3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]-7-(4-piperidinyl)thieno[3,2-c]pyridin-4-amine (37 mg) as a white solid. LC/MS (ES) m/z=469 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 1.64-1.77 (m, 2H), 1.77-1.86 (m, 2H), 2.57-2.77 (m, 3H), 3.07 (d, J=12.13 Hz, 2H), 3.22 (t, J=8.34 Hz, 2H), 3.89 (s, 2H), 4.24 (t, J=8.59 Hz, 2H), 5.24 (br. s., 2H), 7.19-7.39 (m, 7H), 7.41 (s, 1H), 7.70 (s, 1H), 8.15 (d, J=8.34 Hz, 1H)

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. washrinsing with more DCM
  3. concentrationThe filtrate was concentrated in vacuo
  4. customwas purified by flash chromatography (Analogix, 24 g SiO2, DCM to 80/20/2 DCM/MeOH/NH4OH gradient over 30 minutes)

Sources & evidence

ORD record
ord-9cd4aa181fa442a19dbb263b4a29b1e0
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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