(-)-Pseudoephedrine → n1-[(1s,2s)-2-Hydroxy-1-methyl-2-phenylethyl]-n1-methyl-2-[4-amino-3-(4-{[(2,3-dichlorophenyl)sulfonyl]amino}-3-fluorophenyl)-1h-pyrazolo[3,4-d]pyrimidin-1-yl]acetamide

HRID 897663Notes

Reaction equation

HRID 897663 reaction equation
[CH3:1][C@@H:2]([NH:11][CH3:12])[C@H:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[NH2:13][C:14]1[N:19]=[CH:18][N:17]=[C:16]2[N:20]([CH2:42][C:43](OCC)=[O:44])[N:21]=[C:22]([C:23]3[CH:28]=[CH:27][C:26]([NH:29][S:30]([C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[C:34]=4[Cl:40])(=[O:32])=[O:31])=[C:25]([F:41])[CH:24]=3)[C:15]=12>>[OH:10][C@@H:3]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[C@@H:2]([N:11]([CH3:12])[C:43](=[O:44])[CH2:42][N:20]1[C:16]2=[N:17][CH:18]=[N:19][C:14]([NH2:13])=[C:15]2[C:22]([C:23]2[CH:28]=[CH:27][C:26]([NH:29][S:30]([C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[C:34]=3[Cl:40])(=[O:32])=[O:31])=[C:25]([F:41])[CH:24]=2)=[N:21]1)[CH3:1]

Participants

3

Reactant 2

HCID 62946(-)-PseudoephedrineHCID 22346920Ethyl 2-[4-amino-3-(4-{[(2,3-dichlorophenyl)sulfonyl]amino}-3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]acetate

Product 1

HCID 69779620n1-[(1s,2s)-2-Hydroxy-1-methyl-2-phenylethyl]-n1-methyl-2-[4-amino-3-(4-{[(2,3-dichlorophenyl)sulfonyl]amino}-3-fluorophenyl)-1h-pyrazolo[3,4-d]pyrimidin-1-yl]acetamideYield 15%

Procedure

Using a procedure similar to that above, (+)-ephedrine hydrochloride (0.061 g, 0.302 mmol) and ethyl 2-[4-amino-3-(4-{[(2,3-dichlorophenyl)sulfonyl]amino}-3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]acetate (0.054 g, 0.10 mmol) were combined. Purification by preparative HPLC (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 20 min at 21 mL/min using an 8μ Hypersil HS C18, 250×21 mm column, Rt 11.4-11.9 min) afforded N1-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-N1-methyl-2-[4-amino-3-(4-{[(2,3-dichlorophenyl)sulfonyl]amino}-3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]acetamide as an off-white solid (0.010 g, 0.015 mmol): RP-HPLC (25 to 100% CH3CN in 0.1 M aqueous ammonium acetate over 10 min at 1 mL/min using a Hypersil HS C18, 250×4.6 mm column) Rt 9.36 min; MS: (M−H)− 656.

Workup

  1. customPurification by preparative HPLC (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 20 min at 21 mL/min

Sources & evidence

ORD record
ord-40fe9519ccfc44aebed85692cd8cc841
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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