Sodium Hydroxide → ethyl 4-({(2E)-3-[4-amino-3-(3-methoxy-4-{[(1-methyl-1H-indol-2-yl)carbonyl]amino}phenyl)thieno[3,2-c]pyridin-7-yl]prop-2-enyl}amino)piperidine-1-carboxylate

HRID 2390672Notes

Reaction equation

HRID 2390672 reaction equation
[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5](/[CH:32]=[CH:33]/[CH2:34][NH2:35])=[CH:4][N:3]=1.O=[C:37]1[CH2:42][CH2:41][N:40]([C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH2:39][CH2:38]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClC(Cl)C.ClCCl>[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5](/[CH:32]=[CH:33]/[CH2:34][NH:35][CH:37]2[CH2:42][CH2:41][N:40]([C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH2:39][CH2:38]2)=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 34767Ethyl 4-oxo-1-piperidinecarboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 18451029trans-N-(4-(4-amino-7-(3-aminoprop-1-enyl)thieno[3,2-c]pyridin-3-yl)-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide

Product 1

HCID 18450884ethyl 4-({(2E)-3-[4-amino-3-(3-methoxy-4-{[(1-methyl-1H-indol-2-yl)carbonyl]amino}phenyl)thieno[3,2-c]pyridin-7-yl]prop-2-enyl}amino)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a suspension of N-(4-{4-amino-7-[(1E)-3-aminoprop-1-enyl]thieno[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide (0.050 g, 0.104 mmol) and ethyl 4-oxo-1-piperidinecarboxylate (0.017 g, 0.087 mmol) in dichloroethane (1.5 mL) was added sodiumtriacetoxy borohydride (0.036 g, 0.173 mmol). The resulting solution was allowed to stir at room temperature for 12 hours. Upon completion, the reaction solution was treated with an aqueous solution of 10% sodium hydroxide (3 mL) and dichloromethane (3 mL). The two layers were stirred for 15 minutes, followed by filtration through an Empore™ cartridge, and removal of the solvent. The resulting crude product was purified by trituration of the residue in ethanol and collection of the title compound (0.030 g, 45%) as a white powder. LCMS (Conditions a) Rt 3.57 minutes, 639.4 (MH+); 1H NMR (400 MHz, DMSO-d6) δ 9.51 (s, 1H), 8.01 (dd, J=8.2 Hz, J=7.8 Hz, 1H), 7.95 (s, 1H), 7.71 (d, J=8.2 Hz, 1H), 7.62 (s, 1H), 7.59 (d, J=8.2 Hz, 1H), 7.35 (s, 1H), 7.32 (d, J=8.5 Hz, 1H), 7.21 (d, J=1.9 Hz, 1H), 7.15 (t, J=7.8 Hz, 1H), 7.08 (dd, J=8.2 Hz, 1.9 Hz, 1H), 6.67 (d, J=16.0 Hz, 1H), 6.29 (td, J=16.4 Hz, J=5.9 Hz, 1H), 5.61 (s (br), 1H), 4.04 (s, 3H), 4.02 (q, J=7.02 Hz, 2H), 3.91 (s, 3H), 3.88 (m, 2H), 3.42 (d, J=5.5 Hz, 2H), 2.87 (m, 2H), 2.67 (m, 1H), 1.83 (m, 2H), 1.19 (m, 2H), 1.18 (t, J=7.02 Hz, 3H).

Workup

  1. stirringThe two layers were stirred for 15 minutes
  2. filtrationfollowed by filtration through an Empore™ cartridge, and removal of the solvent
  3. customThe resulting crude product was purified by trituration of the residue in ethanol
  4. customcollection of the title compound (0.030 g, 45%) as a white powder

Sources & evidence

ORD record
ord-64b4dd139b0b437ca468e411dce5e984
Source dataset
uspto-grants-2012_09
Patent number
US08273736B2

Reaction notes

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