L-Prolinol → (S)-{1-[2-(4-Piperidin-4-yl-quinazolin-7-yloxy)-ethyl]-pyrrolidin-2-yl}-methanol

HRID 1170238Notes

Reaction equation

C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH2:25][CH2:26]OS(C)(=O)=O)=[CH:21][CH:22]=3)[N:17]=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[NH:32]1[CH2:36][CH2:35][CH2:34][C@H:33]1[CH2:37][OH:38]>CS(C)=O>[NH:8]1[CH2:9][CH2:10][CH:11]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH2:25][CH2:26][N:32]4[CH2:36][CH2:35][CH2:34][C@H:33]4[CH2:37][OH:38])=[CH:21][CH:22]=3)[N:17]=[CH:16][N:15]=2)[CH2:12][CH2:13]1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of 4-[7-(2-methanesulfonyloxy-ethoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester (40.6 mg, 0.09 mmol) in DMSO (0.4 mL) was added (S)-(+)-2-pyrrolidinemethanol (90.9 mg, 0.9 mmol). The mixture was stirred at 120° C. overnight and subsequently partitioned between EtOAc and water. The combined organic extracts were washed with brine, dried over Na2SO4 and evaporated. The residue was treated with 50% TFA/CH2Cl2 (8 mL) for 2 h, the solvents (TFA/CH2Cl2) were removed under reduced pressure to provide the desired product. LC-MS (ESI) calcd for C20H29N4O2 (MH+) 357.2, found 357.2.

Workup

customsubsequently partitioned between EtOAc and water
washThe combined organic extracts were washed with brine
dry with materialdried over Na2SO4
customevaporated
additionThe residue was treated with 50% TFA/CH2Cl2 (8 mL) for 2 h
customthe solvents (TFA/CH2Cl2) were removed under reduced pressure

Sources & evidence

ORD record: ord-c6df735c52e94aad84aa455ae4c706d1
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07825244B2

Reaction notes

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