Hydrochloric Acid → 1-[4-[4-(2-hydroxypropan-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-[(1-methylpyrazol-4-yl)methyl]urea

HRID 2353689Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([C:8]([OH:11])([CH3:10])[CH3:9])[CH:5]=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]2[CH3:18])[N:3]=1.[CH3:19][N:20]1[CH:24]=[C:23]([CH2:25][NH:26][C:27](=[O:44])[NH:28][C:29]2[CH:34]=[CH:33][C:32](B3OC(C)(C)C(C)(C)O3)=[CH:31][CH:30]=2)[CH:22]=[N:21]1.C(=O)([O-])[O-].[Na+].[Na+].Cl>CN(C=O)C.COCCOC.C(O)C.O>[OH:11][C:8]([C:6]1[CH:5]=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]2[CH3:18])[N:3]=[C:2]([C:32]2[CH:33]=[CH:34][C:29]([NH:28][C:27]([NH:26][CH2:25][C:23]3[CH:22]=[N:21][N:20]([CH3:19])[CH:24]=3)=[O:44])=[CH:30][CH:31]=2)[N:7]=1)([CH3:10])[CH3:9]

Participants

Conditions

Temperature: 100 °C

Procedure

2-[2-Chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]propan-2-ol (70 mg) was dissolved in an 18% DMF in a mixture of 7:3:2 DME:water:ethanol (4 mL). 3-[(1-Methylpyrazol-4-yl)methyl]-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea (115 mg) and 2M sodium carbonate (1 mL) were added. Dichlorobis(triphenylphosphine) palladium catalyst (10 mg) was added and the solution heated in a microwave reactor at 100° C. for 0.5 h. The mixture was acidified with concentrated hydrochloric acid and loaded directly onto a SCX-2 column (10 g), column washed with methanol then product eluted with 7N ammonia in methanol, to give the desired material (55 mg) as a white solid.

Workup

washwashed with methanol
washproduct eluted with 7N ammonia in methanol

Sources & evidence

ORD record: ord-687ddb5d0a874e9cab22d7a0beba0f61
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07750003B2

Reaction notes

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