Hydrochloric Acid → HCID 68813499, compound

HRID 2105185Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6](COC)[N:5]=[C:4]([N:11]2[CH2:15][CH2:14][CH2:13][CH:12]2[C:16]2[O:20][N:19]=[C:18]([CH:21]3[CH2:23][CH2:22]3)[CH:17]=2)[N:3]=1.[NH2:24][C:25]1[CH:29]=[C:28]([CH3:30])[NH:27][N:26]=1.Cl.[O:32]1[CH2:37]COC[CH2:33]1>CN1C(=O)CCC1>[CH:21]1([C:18]2[CH:17]=[C:16]([CH:12]3[CH2:13][CH2:14][CH2:15][N:11]3[C:4]3[N:5]=[C:6]([NH:24][C:25]4[CH:29]=[C:28]([CH3:30])[NH:27][N:26]=4)[C:7]([CH2:33][O:32][CH3:37])=[CH:2][N:3]=3)[O:20][N:19]=2)[CH2:22][CH2:23]1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 4-chloro-2-[2-(3-cyclopropylisoxazol-5-yl]pyrrolidin-1-yl]-6-methoxymethylpyrimidine (Method 19) (250 mg, 0.746 mmol), 3-amino-5-methyl-1H-pyrazole (109 mg, 1.2 mmol) and hydrogen chloride (0.56 ml of a 4M solution in dioxane, 2.24 mmol) in NMP (5 ml) was heated at 120° C. for 18 hours. The mixture was allowed to cool then directly applied to an isolute SCX2 ion exchange column. The column was eluted with DCM/methanol (4:1) to remove neutrals and then with 7M methanolic ammonia to elute the product. The partially purified product was then purified by chromatography on silica gel eluting with DCM/methanol (100:0 increasing in polarity to 95:5). The product was triturated with diethyl ether/DCM and the solid product collected by filtration to give the title compound (100 mg, 34%) as a white solid.

Workup

temperatureto cool
washThe column was eluted with DCM/methanol (4:1)
customto remove neutrals
washwith 7M methanolic ammonia to elute the product
customThe partially purified product was then purified by chromatography on silica gel eluting with DCM/methanol (100:0 increasing in polarity to 95:5)
customThe product was triturated with diethyl ether/DCM
filtrationthe solid product collected by filtration

Sources & evidence

ORD record: ord-c6f070b782b049899b74b64c2279dfc4
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07579349B2

Reaction notes

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