Aluminium lithium hydride → HCID 59351221, compound

HRID 555864Notes

Reaction equation

HRID 555864 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10](C(OC(C)(C)C)=O)[C:11]1[CH:40]=[CH:39][C:14]([O:15][C:16]2[C:17]([C:22]3([C:35](OC)=[O:36])[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]3)=[N:18][CH:19]=[CH:20][N:21]=2)=[CH:13][CH:12]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]1[CH:12]=[CH:13][C:14]([O:15][C:16]2[C:17]([C:22]3([CH2:35][OH:36])[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:32])[CH3:33])=[O:29])[CH2:24][CH2:23]3)=[N:18][CH:19]=[CH:20][N:21]=2)=[CH:39][CH:40]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydride2×HCID 59351167HCID 59351167, compound

Product 1

HCID 59351221HCID 59351221, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To an ice cooled solution of 1-tert-butyl 4-methyl 4-(3-(4-(benzo[d]thiazol-2-yl(tert-butoxycarbonyl)amino)phenoxy)pyrazin-2-yl)piperidine-1,4-dicarboxylate (122 mg, 0.184 mmol) in dry THF (5 mL) was added LAH, 2M in THF (0.08 mL, 0.160 mmol). After stirring for 16 hours, LC-MS indicates a mixture of product, starting material, desBoc starting material and desBoc product. The reaction was treated with more LAH, 2M in THF (0.09 mL). After 4 hours, LC-MS shows one main peak that is consistent with desired product minus Boc (m/z 534 MH+). The reaction was quenched with sat'd rochelle's salt and diluted with EtOAc (10 mL). The aqueous layer was extracted with EtOAc (10 mL) and the combined EtOAc layers were concentrated in vacuo. The brown residue was purified by reverse-phase preparative HPLC (Shimadzu) on a Phenomenex Gemini column (5 micron, C18, 110 Å, Axia, 100×50 mm) eluting at 90 mL/min with an linear gradient of 10% to 80% MeCN (0.1% TFA) in water (0.1% TFA) over 20 minutes to give tert-butyl 4-(3-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyrazin-2-yl)-4-(hydroxymethyl)piperidine-1-carboxylate (8.2 mg) as a TFA salt and white solid after lypholization. MS (ESI, pos. ion) m/z: 534.0 (M+1). IC50 (uM) ++++.

Workup

  1. additiona mixture of product
  2. waitAfter 4 hours

Sources & evidence

ORD record
ord-736fbfe7e7e640f4b7cbfddbf570e3f1
Source dataset
uspto-grants-2011_11
Patent number
US08053438B2

Reaction notes

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