Triethylamine → 4-[(4-{[(3-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one Dihydrochloride

HRID 15299

Reaction equation

HRID 15299 reaction equation
C1(N)C(F)=C(F)C(F)=C(N)C=1F.[ClH:13].Cl.[NH2:15][CH:16]1[CH2:21][CH2:20][N:19]([CH2:22][CH:23]2[C:27]3=[CH:28][CH:29]=[N:30][C:31]4[CH:32]=[CH:33][C:34](=[O:35])[N:25]([C:26]=43)[CH2:24]2)[CH2:18][CH2:17]1.C(N(CC)CC)C.[O:43]=[C:44]1[CH2:49][S:48][C:47]2[CH:50]=[CH:51][C:52]([CH:54]=O)=[N:53][C:46]=2[NH:45]1.[BH4-].[Na+]>CO.ClCCl>[ClH:13].[ClH:13].[O:43]=[C:44]1[CH2:49][S:48][C:47]2[CH:50]=[CH:51][C:52]([CH2:54][NH:15][CH:16]3[CH2:21][CH2:20][N:19]([CH2:22][CH:23]4[C:27]5=[CH:28][CH:29]=[N:30][C:31]6[CH:32]=[CH:33][C:34](=[O:35])[N:25]([C:26]=65)[CH2:24]4)[CH2:18][CH2:17]3)=[N:53][C:46]=2[NH:45]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 4311764Sodium borohydrideHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 686849574-[(4-amino-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one

Product 1

HCID 686857044-[(4-{[(3-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one DihydrochlorideYield 41%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of the dihydrochloride salt of 4-[(4-amino-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one (56 mg, 0.158 mmol) in methanol (0.4 ml), dichloromethane (1.6 ml) was added triethylamine (110 μl, 0.79 mmol) and 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxaldehyde (for a synthesis see WO2003087098, Example 301(d)) (31 mg, 0.158 mmol). This mixture was stirred for 18 h at 25° C. before NaBH4 (6 mg, 0.158 mmol) was added and the reaction stirred for a further 0.5 h after which time the solvent was evaporated and the residue was subjected to column chromatography on silica gel using a 0-30% methanol in dichloromethane gradient. This provided the free base of the title compound as a yellow solid (30 mg, 41%).

Workup

  1. additionwas added
  2. customwas evaporated

Sources & evidence

ORD record
ord-93683e7a8f8b487196d2d9f3d2f60195
Source dataset
uspto-grants-2010_06
Patent number
US07732461B2

Linked notes

Loading…