8-(1-(2-(tert-butyldimethylsilyloxy)ethyl)-1H-pyrazol-3-ylamino)-6-chloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide → HCID 178511635, compound

HRID 1943471Notes

Reaction equation

[Si]([O:8][CH2:9][CH2:10][N:11]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[C:18]3[N:19]([C:24]([C:27]([NH:29][C:30]4[CH:35]=[CH:34][N:33]=[CH:32][C:31]=4[F:36])=[O:28])=[CH:25][N:26]=3)[N:20]=[C:21](Cl)[CH:22]=2)=[N:12]1)(C(C)(C)C)(C)C.[C@H:37]1([NH2:44])[CH2:42][CH2:41][C@H:40]([NH2:43])[CH2:39][CH2:38]1>CN1C(=O)CCC1>[NH2:43][C@H:40]1[CH2:41][CH2:42][C@H:37]([NH:44][C:21]2[CH:22]=[C:17]([NH:16][C:13]3[CH:14]=[CH:15][N:11]([CH2:10][CH2:9][OH:8])[N:12]=3)[C:18]3[N:19]([C:24]([C:27]([NH:29][C:30]4[CH:35]=[CH:34][N:33]=[CH:32][C:31]=4[F:36])=[O:28])=[CH:25][N:26]=3)[N:20]=2)[CH2:38][CH2:39]1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 50A (40 mg, 0.075 mmol) and trans-cyclohexane-1,4-diamine (86 mg, 0.753 mmol) in NMP (0.5 mL) was heated at 110° C. overnight. The reaction mixture was cooled to room temperature and purified by reversed-phase preparative HPLC. The desired fractions were concentrated and dried to give 50B (19.3 mg, 51%) as a beige solid. HPLC Rt=2.037 min (Chromolith SpeedROD 4.6×50 mm, 10-90% aqueous methanol containing 0.1% TFA, 4 min gradient, monitored at 220 nm), [M+H]=495.

Workup

temperatureThe reaction mixture was cooled to room temperature
custompurified by reversed-phase preparative HPLC
concentrationThe desired fractions were concentrated
customdried

Sources & evidence

ORD record: ord-045c84bb6f0540ed964c8c9ec2679e06
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08389527B2

Reaction notes

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