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

HRID 2353694Notes

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.[O:19]1[CH:23]=[CH:22][C:21]([NH:24][C:25](=[O:42])[NH:26][C:27]2[CH:32]=[CH:31][C:30](B3OC(C)(C)C(C)(C)O3)=[CH:29][CH:28]=2)=[N:20]1.CN(C=O)C.Cl>C(O)C.O.COCCOC>[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:30]2[CH:29]=[CH:28][C:27]([NH:26][C:25]([NH:24][C:21]3[CH:22]=[CH:23][O:19][N:20]=3)=[O:42])=[CH:32][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 (160 mg, 0.59 mmol) was added to 3-(1,2-oxazol-3-yl)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea (242 mg) and Dichlorobis(triphenylphosphine) palladium catalyst (21 mg) in an 18% DMF in a mixture of 7:3:2 DME:water:ethanol (6 mL). The reaction was heated to 100° C. for 30 minutes in the microwave reactor and cooled to RT. The reaction mixture was acidified with 2M hydrochloric acid and the crude material loaded onto a SCX (10 g) column, the desired material was eluted with 7N ammonia in methanol. The material was further purified by preparative HPLC using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents, to give the desired material (52 mg) as a white solid.

Workup

temperaturecooled to RT
washthe desired material was eluted with 7N ammonia in methanol
customThe material was further purified by preparative HPLC

Sources & evidence

ORD record: ord-1511b3c5c0e243a8b68fbae00ab2ae77
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07750003B2

Reaction notes

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