tert-butyl N-(6-aminoisoquinolin-1-yl)-N-[(tert-butoxy)carbonyl]carbamate → di-tert-butyl (6-{[(4-bromo-1-trityl-1H-imidazol-2-yl) (5-ethyl-2-fluoro-3-(2-oxopyrrolidin-1-yl)phenyl)methyl]amino}isoquinolin-1-yl)imidodicarbonate

HRID 2105075Notes

Reaction equation

HRID 2105075 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([CH:26]([NH:38][C:39]2[CH:40]=[C:41]3[C:46](=[CH:47][CH:48]=2)[C:45]([N:49]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])=[N:44][CH:43]=[CH:42]3)[C:27]2[CH:32]=[C:31]([CH2:33][CH3:34])[CH:30]=[C:29](OC)[C:28]=2[F:37])[N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1.BrC1N=C(C(O)C2C(F)=C([N:98]3[CH2:102][CH2:101][CH2:100][C:99]3=[O:103])C=C(CC)C=2)N(C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=1.BrC1N=C(C(Cl)C2C=C(CC)C=C(OC)C=2F)N(C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=1.NC1C=C2C(=CC=1)C(N(C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=NC=C2>>[Br:1][C:2]1[N:3]=[C:4]([CH:26]([NH:38][C:39]2[CH:40]=[C:41]3[C:46](=[CH:47][CH:48]=2)[C:45]([N:49]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[C:57]([O:59][C:60]([CH3:62])([CH3:63])[CH3:61])=[O:58])=[N:44][CH:43]=[CH:42]3)[C:27]2[CH:32]=[C:31]([CH2:33][CH3:34])[CH:30]=[C:29]([N:98]3[CH2:102][CH2:101][CH2:100][C:99]3=[O:103])[C:28]=2[F:37])[N:5]([C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:6]=1

Participants

5

Reactant 4

HCID 58717298tert-butyl N-(6-aminoisoquinolin-1-yl)-N-[(tert-butoxy)carbonyl]carbamateHCID 688130341-(3-((4-bromo-1-trityl-1H-imidazol-2-yl)(hydroxy)methyl)-5-ethyl-2-fluorophenyl)pyrrolidin-2-oneHCID 688168844-bromo-2-(chloro(5-ethyl-2-fluoro-3-methoxyphenyl)methyl)-1-trityl-1H-imidazoleHCID 86607941di-tert-butyl (6-{[(4-bromo-1-trityl-1H-imidazol-2-yl)(5-ethyl-2-fluoro-3-methoxyphenyl)methyl]amino}isoquinolin-1-yl)imidodicarbonate

Product 1

HCID 86607945di-tert-butyl (6-{[(4-bromo-1-trityl-1H-imidazol-2-yl) (5-ethyl-2-fluoro-3-(2-oxopyrrolidin-1-yl)phenyl)methyl]amino}isoquinolin-1-yl)imidodicarbonate

Procedure

According to the procedure for the preparation of Intermediate 206.4, Intermediate 398.3 (65 mg, 0.104 mmol) was converted to the chloro intermediate, then displaced with di-tert-butyl (6-aminoisoquinolin-1-yl)imidodicarbonate (rt for 14 h) to afford after flash chromatography (0 to 100% EtOAc/hexanes gradient) 53.3 mg of Intermediate 398.4 as a colorless solid. LCMS (2 min gradient) RT=2.14 min, 723.1 (M+(H−Tr)+H)+.

Sources & evidence

ORD record
ord-de5de1de786f4dfd9e4c6939aa28e91e
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

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