4-Fluorophenylacetyl chloride → tert-Butyl 6-(2-fluoro-4-(3-(4-fluorophenylamino)-3-oxopropanamido)phenoxy)pyrimidin-4-yl(methyl)carbamate

HRID 2237168Notes

Reaction equation

HRID 2237168 reaction equation
[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[N:12]=[CH:11][N:10]=[C:9]([N:13]([CH3:21])[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH:8]=2)=[C:4]([F:24])[CH:3]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29](CC(Cl)=O)=[CH:28][CH:27]=1.Cl[C:37]1[N:42]=CN=[C:39]([O:43]C2C=CC(NC(NC(=O)CC3C=CC(F)=CC=3)=S)=CC=2F)[CH:38]=1.CC[O:67]C(C)=O.C(Cl)Cl>>[F:24][C:4]1[CH:3]=[C:2]([NH:1][C:39](=[O:43])[CH2:38][C:37]([NH:42][C:29]2[CH:28]=[CH:27][C:26]([F:25])=[CH:31][CH:30]=2)=[O:67])[CH:23]=[CH:22][C:5]=1[O:6][C:7]1[N:12]=[CH:11][N:10]=[C:9]([N:13]([CH3:21])[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH:8]=1

Participants

5

Reactant 4

HCID 37449884-Fluorophenylacetyl chlorideHCID 115538441-(4-(6-Chloropyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)thioureaHCID 21226138Dichloromethane ethylacetateHCID 59853009tert-Butyl 6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl(methyl)carbamate

Product 1

HCID 11642036tert-Butyl 6-(2-fluoro-4-(3-(4-fluorophenylamino)-3-oxopropanamido)phenoxy)pyrimidin-4-yl(methyl)carbamateYield 83%

Procedure

The title compound was prepared from tert-butyl 6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl(methyl)carbamate (30 mg, 0.068 mmol), 4-fluorophenylacetyl chloride (Lancaster, 15 mg, 0.088 mmol) and NaSCN (9 mg, 0.11 mmol) in EtOAc/CH2Cl2 using a similar procedure described for the preparation of Compound C of Example 2. Flash chromatography on SiO2 using 1-40% EtOAc in hexanes as the eluent gave the title compound (30 mg, 83%) as a white solid. 1H NMR (DMSO-d6) δ 12.40 (s, 1H), 11.79 (s, 1H), 8.55 (s, 1H), 7.86 (dd, 1H, J=12.1, 2.5 Hz), 7.54 (d, 1H, J=1.1 Hz), 7.45-7.35 (m, 4H), 7.20-7.14 (ddd, 2H, J=8.8, 8.8, 2.1 Hz), 3.81 (s, 2H), 3.36 (s, 3H), 1.49 (s, 9H); MS(ESI+) m/z 530.09 (M+H)+.

Sources & evidence

ORD record
ord-d8447eb3d8c847a4acd25862a2e3281e
Source dataset
uspto-grants-2010_05
Patent number
US07714138B2

Reaction notes

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