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Sodium Hydroxide → HCID 136333947, compound

HRID 1052211
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Reaction equation

HRID 1052211 reaction equation
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]([CH:12]3[CH:21]4[CH:16]([CH2:17][CH2:18][CH2:19][CH2:20]4)[CH2:15][CH2:14][N:13]3C(OC(C)(C)C)=O)=[N:5][C:4]=2[CH:3]=1.[NH2:29][C:30]1[CH:34]=C(Br)S[C:31]=1[C:36]([NH2:38])=O.C(OC(N1CC2CC1(C(O)=O)C2)=O)(C)(C)C.C([Cl:62])(=O)OCC(C)C.[OH-].[Na+]>CO.O1CCCC1.C(N(CC)CC)C>[ClH:62].[CH:12]1([C:6]2[NH:7][C:8](=[O:11])[C:9]3[S:10][C:2]([C:31]4[CH:36]=[N:38][NH:29][C:30]=4[CH3:34])=[CH:3][C:4]=3[N:5]=2)[CH:21]2[CH:16]([CH2:17][CH2:18][CH2:19][CH2:20]2)[CH2:15][CH2:14][NH:13]1
ParticipantsProcedureSources & evidenceReaction notes

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 62365Isobutyl chloroformateHCID 12127697N-(t-butoxycarbonyl)-1-carboxy-2-azabicyclo[2.1.1]hexaneHCID 219758623-Amino-5-bromothiophene-2-carboxamideHCID 136333949HCID 136333949, compound

Product 1

HCID 136333947
HCID 136333947, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

In the same manner as in Example 71, step A, tert-butyl 1-(6-bromo-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)octahydroisoquinoline-2 (1H)-carboxylate (180 mg) as a colorless solid from 3-amino-5-bromothiophene-2-carboxamide (0.22 g) produced in Example 1, step D, 2-(tert-butoxycarbonyl)-2-azabicyclo[2.1.1]hexane-1-carboxylic acid (0.57 g), 2-methylpropyl chlorocarbonate (0.27 g), triethylamine (0.20 g) and tetrahydrofuran (10 mL), and 2M aqueous sodium hydroxide solution (1 mL) and methanol (5 mL). In the same manner as in Example 83, step C, 2-(decahydroisoquinolin-1-yl)-6-(5-methyl-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-4 (3H)-one hydrochloride was obtained from the compound obtained above, tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (270 mg), cesium carbonate (290 mg), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane complex (1:1)(18 mg), 1,2-dimethoxyethane (10 mL), water (1 mL), and 4M hydrochloric acid/ethyl acetate solution (2 mL) and methanol (10 mL). This was purified by basic silica gel column chromatography (methanol/ethyl acetate) to give the title compound (36 mg) as a colorless solid.

Sources & evidence

ORD record
ord-cc4080d345b14cf5932dd64e22a1cfbe
Source dataset
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09388195B2

Reaction notes

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