2-tert-butylimino-N,N-diethyl-1-methyl-1,3,2lambda5-diazaphosphinan-2-amine → 3-(1-Amino-isoquinolin-6-yloxy)piperidin-1--carboxylic acid tert-butyl ester

HRID 1435964Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([O:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[C:21]([NH2:25])=[N:20][CH:19]=[CH:18]3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].NC1C2C(=CC(O)=CC=2)C=CN=1.C(OC(N1CCC[C@@H](OS(C)(=O)=O)C1)=O)(C)(C)C.CCN(P1(N(C)CCCN1)=NC(C)(C)C)CC>C(#N)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([O:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[C:21]([NH2:25])=[N:20][CH:19]=[CH:18]3)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 160 °C

Procedure

For an alternate procedure for the preparation of (S)-3-(1-amino-isoquinolin-6-yloxy)piperidin-1-carboxylic acid tert-butyl ester, a suspension of 1-amino-6-hydroxyisoquinoline (0.8 g, 5.0 mmol), (R)-3-methanesulfonyloxypiperidine-1-carboxylic acid tert-butyl ester (1.76 g) and 2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine on polystyrene (3.4 g, −2.2 mmol/g loading) in acetonitrile (10 ml) were heated at 160° C. over a period of 15 minutes using the microwave. The excess supported regent was removed by filtration, washing with acetonitrile followed by methanol, and the filtrate evaporated to dryness under reduced pressure. Purification was achieved by chromatography on silica (eluent: 2-10% methanol in ethyl acetate) to afford (S) 3-(1-amino-isoquinolin-6-yloxy)piperidin-1-carboxylic acid tert-butyl ester (72 mg), El-MS: m/z=344.1 [M+H]+.

Workup

customwas removed by filtration
washwashing with acetonitrile
customthe filtrate evaporated to dryness under reduced pressure
customPurification

Sources & evidence

ORD record: ord-a9ac1a8cca5946bd8943abe5ba2d0eaa
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07618985B2

Reaction notes

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