3-Carboxyphenylboronic acid → (6-Biphenyl-4-yl-2-methoxy-pyrimidin-4-yl)-[2-(3,4-dimethoxy-phenyl)-ethyl]-amine

HRID 216141Notes

Reaction equation

HRID 216141 reaction equation
CS([C:5]1[CH:6]=[C:7]([C:11]2[N:16]=[C:15]([O:17][CH3:18])[N:14]=[C:13]([NH:19][CH2:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=O)=O.ClC1N=C(OC)N=C(NCC[C:42]2[CH:47]=[CH:46][C:45](OC)=[C:44](OC)[CH:43]=2)C=1.ClC1N=[C:57]([O:59]C)N=C(NCCC2C=CC(OC)=CC=2)C=1.C(C1C=C(B(O)O)C=CC=1)(O)=O>>[C:10]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:9]=[CH:8][C:7]([C:11]2[N:16]=[C:15]([O:17][CH3:18])[N:14]=[C:13]([NH:19][CH2:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([O:59][CH3:57])[CH:23]=3)[CH:12]=2)=[CH:6][CH:5]=1

Participants

5

Reactant 4

HCID 27339573-Carboxyphenylboronic acidHCID 11582363[6-(3-Methanesulfonyl-phenyl)-2-methoxy-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amineHCID 57636025(6-Chloro-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxyphenyl)-ethyl]amineHCID 576361256-Chloro-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-methoxy-4-pyrimidinamine

Product 1

HCID 11611955(6-Biphenyl-4-yl-2-methoxy-pyrimidin-4-yl)-[2-(3,4-dimethoxy-phenyl)-ethyl]-amine

Procedure

By proceeding in a similar manner as above in Example 35(a) but (i) substituting (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(3,4-dimethoxy-phenyl)-ethyl]-amine [100 mg, Intermediate (42)] for (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxy-phenyl)-ethyl]-amine, and (ii) substituting 4-Biphenylboronic acid (122 mg) for 3-carboxyphenyl boronic acid, and (iii) subjecting the crude reaction product to flash column chromatography on silica (10 g) eluting with 20 to 60% EtOAc in heptane gradient, there is prepared (6-biphenyl-4-yl-2-methoxy-pyrimidin-4-yl)-[2-(3,4-dimethoxy-phenyl)-ethyl]-amine [79.7 mg, 58.6%, Example 35(e)]. LCMS: RT=3.05 minutes, MS: 442 (M+H). 1H NMR (300 MHz, CDCl3) δ 8.36 (1H, d, J=0.027 Hz), 8.09 (2H, d, J=0.027 Hz), 7.84 (1H, d, J=0.027 Hz), 7.78 (1H, d, J=0.027 Hz), 7.68 (9H, m), 7.45 (4H, m), 6.84 (1H, t, J=0.027 Hz), 6.79 (2H, m), 6.44 (1H, s), 4.93 (1H, s), 4.77 (1H, s), 4.07 (3H, s), 3.9 (6H, s), 3.72 (2H, m), 2.94 (2H, t, J=0.022 Hz). IC50=369 nM

Workup

  1. customreaction product to flash column chromatography on silica (10 g)
  2. washeluting with 20 to 60% EtOAc in heptane gradient, there
  3. customis prepared (6-biphenyl-4-yl-2-methoxy-pyrimidin-4-yl)-[2-(3,4-dimethoxy-phenyl)-ethyl]-amine [79.7 mg, 58.6%, Example 35(e)]

Sources & evidence

ORD record
ord-4c79c5bf388f4af68c8a6a162cac9d96
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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