Sodium Hydroxide → 4-[4-(2-{1-[2-(Tert-butyl-dimethyl-silanyloxy)-ethylcarbamoyl]-1-methyl-ethoxy}-phenoxy)-phenylamino]-3-cyano-5-methyl-pyrrolo[1,2-b]pyridazine-6-carboxylic acid

HRID 1796686Notes

Reaction equation

HRID 1796686 reaction equation
[C:1]([C:3]1[CH:8]=[N:7][N:6]2[CH:9]=[C:10]([C:13]([OH:15])=[O:14])[C:11]([CH3:12])=[C:5]2[C:4]=1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[O:30][C:31]([C:34](=[O:39])[NH:35][CH2:36][CH2:37][OH:38])([CH3:33])[CH3:32])=[CH:19][CH:18]=1)#[N:2].CCN(C(C)C)C(C)C.[CH3:49][C:50]([Si:53](Cl)([CH3:55])[CH3:54])([CH3:52])[CH3:51].[OH-].[Na+]>CN(C1C=CN=CC=1)C.C1COCC1>[C:50]([Si:53]([CH3:55])([CH3:54])[O:38][CH2:37][CH2:36][NH:35][C:34]([C:31]([CH3:33])([O:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[O:23][C:20]1[CH:19]=[CH:18][C:17]([NH:16][C:4]2[C:5]3[N:6]([CH:9]=[C:10]([C:13]([OH:15])=[O:14])[C:11]=3[CH3:12])[N:7]=[CH:8][C:3]=2[C:1]#[N:2])=[CH:22][CH:21]=1)[CH3:32])=[O:39])([CH3:52])([CH3:51])[CH3:49]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 28928tert-Butyldimethylsilyl chlorideHCID 81531DiisopropylethylamineHCID 22179504HCID 22179504, compound

Product 1

HCID 221796374-[4-(2-{1-[2-(Tert-butyl-dimethyl-silanyloxy)-ethylcarbamoyl]-1-methyl-ethoxy}-phenoxy)-phenylamino]-3-cyano-5-methyl-pyrrolo[1,2-b]pyridazine-6-carboxylic acidYield 38%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 433F (164 mg, 0.31 mmol), DIEA (0.27 ml, 1.55 mmol), DMAP (7.6 mg, 0.062 mmol) and TBSCl (140 mg, 0.93 mmol) in THF (4 ml) was stirred under argon at rt for 2 h. 1N NaOH (0.70 ml, 0.70 mmol) was added. The resulting mixture was stirred at rt for 1 h. Removal of the solvent followed by flash chromatography of the residue of silica gel (2%-5% MeOH—CH2Cl2) gave 433G (75 mg, 38%) as a yellow oil. It has a retention time of 7.43 min (standard LC1 method, 8 min run). MS Found: (M+H)+=644.0

Workup

  1. customRemoval of the solvent

Sources & evidence

ORD record
ord-1c9608d58def46baba82465c1bc95964
Source dataset
uspto-grants-2006_04
Patent number
US07030112B2

Reaction notes

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