Tetrahydrofuran → N-(5-Bromo-pyridin-2-yl)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-4-{4-[3-((R)-1-phenyl-ethyl)-ureido]-phenylsulfanyl}-benzamide

HRID 605327Notes

Reaction equation

HRID 605327 reaction equation
ClC(Cl)(Cl)C[O:4][C:5](=O)[NH:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:19]=[CH:18][C:17]([C:20](=[O:29])[NH:21][C:22]3[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][N:23]=3)=[CH:16][C:15]=2[NH:30][C:31]2[C:32]3[CH:40]=[CH:39][C:38]([CH:41]([CH3:43])[CH3:42])=[N:37][C:33]=3[N:34]=[CH:35][N:36]=2)=[CH:9][CH:8]=1.[CH3:47][C@@H:48]([NH2:55])[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1.[O:56]1CCCC1>>[C:20]([O-:29])(=[O:56])[CH3:17].[NH4+:6].[Br:28][C:25]1[CH:26]=[CH:27][C:22]([NH:21][C:20](=[O:29])[C:17]2[CH:18]=[CH:19][C:14]([S:13][C:10]3[CH:9]=[CH:8][C:7]([NH:6][C:5]([NH:55][C@@H:48]([C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=4)[CH3:47])=[O:4])=[CH:12][CH:11]=3)=[C:15]([NH:30][C:31]3[C:32]4[CH:40]=[CH:39][C:38]([CH:41]([CH3:43])[CH3:42])=[N:37][C:33]=4[N:34]=[CH:35][N:36]=3)[CH:16]=2)=[N:23][CH:24]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 6431891-Phenethylamine, (+)-HCID 67040673{4-[4-(5-Bromo-pyridin-2-ylcarbamoyl)-2-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-phenylsulfanyl]-phenyl}-carbamic acid 2,2,2-trichloro-ethyl ester

Product 2

HCID 517165Ammonium AcetateHCID 67040949N-(5-Bromo-pyridin-2-yl)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-4-{4-[3-((R)-1-phenyl-ethyl)-ureido]-phenylsulfanyl}-benzamideYield 14%

Conditions

Temperature
60 °C

Procedure

The product of Example 364E (152 mg, 0.2 mmol) in tetrahydrofuran (2 mL) was treated with 1,8-diazobicyclo[5.4.0]undec-7-ene (60 μL, 0.4 mm01) and (R)-(+)-α-methylbenzylamine (121 mg, 1.0 mmol) and heated at 60° C. for 1 hour in a sealed tube. The reaction mixture was cooled, concentrated and the residue was purified by preparative HPLC on a Waters Symmetry C8 column (40 mm×100 mm, 7 um particle size) using a gradient of 10% to 100% acetonitrile: aqueous ammonium acetate (10 mM) over 12 min (15 min run time) at a flow rate of 70 mL/min to give the title compound (21 mg, 14%). 1H NMR (300 MHz, DMSO-D6) δ ppm: 1.33 (d, J=6.99 Hz, 6 H) 1.40 (d, J=6.62 Hz, 3 H) 3.22 (m, 1 H) 4.82 (m, 1 H) 6.73 (d, J=8.09 Hz, 1 H) 6.90 (s, br, 1 H) 7.24 (m, 1 H) 7.35 (m, 6 H) 7.48 (m, 2 H) 7.63 (s, br, 1 H) 7.86 (s, br, 1 H) 8.04 (d, J=2.57 Hz, 1 H) 8.07 (d, J=2.57 Hz, 1 H) 8.17 (m, 1 H) 8.49 (d, J=2.57 Hz, 1 H) 8.60 (s, 1 H) 8.66 (s, 1 H) 8.86 (s, br, 1 H) 10.28 (s, 1 H) 10.95 (s, 1 H); (ESI+) m/z 733 735 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated
  3. customthe residue was purified by preparative HPLC on a Waters Symmetry C8 column (40 mm×100 mm, 7 um particle size)

Sources & evidence

ORD record
ord-c54e0fc5b78341ba8fee97f6133def7f
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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