4-[(5-{(1R)-2-[allyl(methyl)amino]-1-methylethoxy}quinazolin-4-yl)amino]-2-chlorophenol → 2-chloro-4-({5-[(1R)-1-methyl-2-(methylamino)ethoxy]quinazolin-4-yl}amino)phenol

HRID 1864199Notes

Reaction equation

[CH2:1]([N:4](C)[CH2:5][C@@H:6]([CH3:27])[O:7][C:8]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:9]=1[C:10]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([OH:25])=[C:21]([Cl:26])[CH:20]=1)=[N:11][CH:12]=[N:13]2)C=C>C(#N)C.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh]>[Cl:26][C:21]1[CH:20]=[C:19]([NH:18][C:10]2[C:9]3[C:14](=[CH:15][CH:16]=[CH:17][C:8]=3[O:7][C@H:6]([CH3:27])[CH2:5][NH:4][CH3:1])[N:13]=[CH:12][N:11]=2)[CH:24]=[CH:23][C:22]=1[OH:25]

Participants

Conditions

Temperature: 130 °C

Procedure

Chlorotris(triphenylphosphine)rhodium(I) (40 mg) was added to a solution of 4-[(5-{(1R)-2-[allyl(methyl)amino]-1-methylethoxy}quinazolin-4-yl)amino]-2-chlorophenol (841 mg) in acetonitrile/water (5:1, 4 ml), and the mixture heated to 130° C. for 10 minutes by microwave irradiation. The cooled mixture was subjected to ion exchange chromatography and product eluted with methanol/2M ammonia yielding 2-chloro-4-({5-[(1R)-1-methyl-2-(methylamino)ethoxy]quinazolin-4-yl}amino)phenol as a brown solid (776 mg, 100%); NMR spectrum (DMSO-d6) 1.40 (d, 3H), 2.33 (s, 3H), 2.87 (m, 2H), 3.29 (1H obscured by water), 4.88 (m, 1H), 6.97 (d, 1H), 7.14 (d, 1H), 7.28 (d, 1H), 7.55 (dd, 1H), 7.68 (t, 1H), 7.95 (d, 1H), 8.45 (s, 1H), 10.51 (bs, 1H); Mass spectrum MH+ 359.

Workup

washeluted with methanol/2M ammonia

Sources & evidence

ORD record: ord-e42d3cde8cce44359b8b0d560c9e93a2
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07625908B2

Reaction notes

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