Diisopropylethylamine → 4-Hydroxy-4-(4-{7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-3-methoxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1262119Notes

Reaction equation

HRID 1262119 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:15]2[CH:20]=[CH:19][C:18]([NH2:21])=[C:17]([O:22][CH3:23])[CH:16]=2)([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][S:25]([N:28]([CH3:52])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]1[N:43]2[C:38]([CH:39]=[N:40][C:41](OS(C(F)(F)F)(=O)=O)=[N:42]2)=[CH:37][CH:36]=1)(=[O:27])=[O:26].C(N(CC)C(C)C)(C)C>COCC(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([OH:14])([C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:41]3[N:40]=[CH:39][C:38]4=[CH:37][CH:36]=[C:35]([C:30]5[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=5[N:28]([S:25]([CH3:24])(=[O:27])=[O:26])[CH3:52])[N:43]4[N:42]=3)=[C:17]([O:22][CH3:23])[CH:16]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 667109494-(4-Amino-3-methoxy-phenyl)-4-hydroxy-piperidine-1-carboxylic acid tert-butyl esterHCID 86661681Trifluoro-methanesulfonic acid 7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester

Product 1

HCID 667114924-Hydroxy-4-(4-{7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-3-methoxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 79001-Methoxy-2-propanolSolvent

Conditions

Temperature
100 °C

Procedure

4-(4-Amino-3-methoxy-phenyl)-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (50 mg, 1.0 equiv), trifluoromethanesulfonic acid 7-[2-(methanesulfonyl-methyl-amino)-phenyl]pyrrolo[2,1-f][1,2,4]triazin-2-yl ester (70 mg, 1.0 equiv) and N,N-diisopropylethylamine (54 1, 2.0 equiv) were dissolved in 1-methoxy-2-propanol, and heated to 100° C. overnight. Concentrated, and purified by preparative TLC, 60% EtOAc/hexane containing 1% triethylamine. Obtained 4-hydroxy-4-(4-{7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-3-methoxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester as a brown solid, 43 mg. mp 111-112° C. LCMS (E/I+) 623 (M+H). NMR 1H (CDCl3) 8.71 (s, 1H), 8.12 (d, J=4.74 Hz, 1H), 7.90-7.96 (m, 1H), 7.46-7.58 (m, 3H), 7.00-7.05 (m, 2H), 6.79-6.89 (m, 2H), 3.96-4.11 (m, 2H), 3.89 (s, 3H), 3.17-3.29 (m, 2H), 3.12 (s, 3H), 2.66 (s, 3H), 1.85-2.01 (m, 2H), 1.58-1.67 (m, 2H), 1.60 (s, 1H), 1.50 (s, 9H).

Workup

  1. concentrationConcentrated
  2. custompurified by preparative TLC, 60% EtOAc/hexane containing 1% triethylamine

Sources & evidence

ORD record
ord-52b2efba86b948779e1e64c5604bcb99
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

Loading…