Diisopropylethylamine → [(2R)-3-{2-[6-(1-azetidinyl)-5-fluoro-2-(methylthio)-4-pyrimidinyl]hydrazino}-2-(cyclopentylmethyl)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamide

HRID 1366391Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([NH:10][NH:11][C:12](=[O:31])[C@H:13]([CH2:25][CH:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)[CH2:14][N:15]([O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[CH:16]=[O:17])[C:3]=1[F:32].Cl.[NH:34]1[CH2:37][CH2:36][CH2:35]1.CCN(C(C)C)C(C)C>CS(C)=O>[N:34]1([C:2]2[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([NH:10][NH:11][C:12](=[O:31])[C@H:13]([CH2:25][CH:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)[CH2:14][N:15]([O:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[CH:16]=[O:17])[C:3]=2[F:32])[CH2:37][CH2:36][CH2:35]1

Participants

Conditions

Temperature: 67.5 °C

Procedure

To a pressure tube was added [(2R)-3-{2-[6-chloro-5-fluoro-2-(methylthio)-4-pyrimidinyl]hydrazino}-2-(cyclopentylmethyl)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamide (0.100 g, 0.204 mmol), azetidine hydrochloride (19.1 mg, 0.204 mmol), DIPEA (71.2 μL, 0.408 mmol) and DMSO (2 mL). The tube was sealed and was heated to 65-70° C. with stirring for 3 days. The reaction mixture was then cooled to RT and purified by RP-HPLC to afford [(2R)-3-{2-[6-(1-azetidinyl)-5-fluoro-2-(methylthio)-4-pyrimidinyl]hydrazino}-2-(cyclopentylmethyl)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamide (68 mg, 65%). LCMS: (M+H)+: 511.2.

Workup

customThe tube was sealed
temperatureThe reaction mixture was then cooled to RT
custompurified by RP-HPLC

Sources & evidence

ORD record: ord-ece280a9d7304ef9bcecce0de49b0bee
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07893056B2

Reaction notes

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