Potassium Carbonate → 4-(5-{3-[(4-Cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one

HRID 1028119Notes

Reaction equation

HRID 1028119 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[S:13][C:12]([N:14]3[CH2:20][CH2:19][CH2:18][NH:17][C:16](=[O:21])[CH2:15]3)=[N:11][CH:10]=2)[CH:5]=[C:6]([CH3:8])[CH:7]=1.Cl[C:23]1[N:28]=[C:27]([CH:29]2[CH2:31][CH2:30]2)[CH:26]=[CH:25][N:24]=1.C(=O)([O-])[O-].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:29]1([C:27]2[CH:26]=[CH:25][N:24]=[C:23]([NH:1][C:2]3[CH:3]=[C:4]([C:9]4[S:13][C:12]([N:14]5[CH2:20][CH2:19][CH2:18][NH:17][C:16](=[O:21])[CH2:15]5)=[N:11][CH:10]=4)[CH:5]=[C:6]([CH3:8])[CH:7]=3)[N:28]=2)[CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 249019152-Chloro-4-cyclopropylpyrimidineHCID 67236328HCID 67236328, compound2×

Product 1

HCID 683243374-(5-{3-[(4-Cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-oneYield 72%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

In an oven-dried vial was added 4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one (Intermediate XX, 77 mg, 0.26 mmol), 2-chloro-4-cyclopropylpyrimidine (44 mg, 0.26 mmol), potassium carbonate (70 mg, 0.51 mmol), XPhos (61 mg, 0.13 mmol), and Pd2(dba)3 (23 mg, 0.025 mmol). The tube was evacuated and backfilled with argon 3×. Degassed t-amyl alcohol (0.85 ml) was added, and the tube was sealed and heated to 90° C. for 15 h. The mixture was then cooled to room temperature and purified by Combiflash (0-70% ethyl acetate/hexanes followed by 0-20% methanol/dichloromethane) to provide 77 mg (0.18 mmol, 72%) of 4-(5-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one as a yellow foam. MS APCI: [M+H]+ m/z 421.2. 1H NMR (500 MHz, CDCl3) δ 8.16 (d, J=5.6 Hz, 1H), 7.75 (s, 1H), 7.44 (s, 2H), 7.13 (s, 1H), 6.91 (s, 1H), 6.65 (d, J=5.5 Hz, 1H), 6.00 (s, 1H), 4.27 (d, J=13.9 Hz, 2H), 3.98-3.79 (m, 2H), 3.38 (dd, J=5.6 Hz, 11.2 Hz, 2H), 2.33 (s, 3H), 2.04 (d, J=4.0 Hz, 3H), 1.26 (t, J=7.3 Hz, 2H), 1.11 (dd, J=3.2 Hz, 8.3 Hz, 2H). rhSyk=+++.

Workup

  1. customThe tube was evacuated
  2. additionDegassed t-amyl alcohol (0.85 ml) was added
  3. customthe tube was sealed
  4. temperatureThe mixture was then cooled to room temperature
  5. custompurified by Combiflash (0-70% ethyl acetate/hexanes followed by 0-20% methanol/dichloromethane)

Sources & evidence

ORD record
ord-c3e6f840f8914a41bdcedd7724867e79
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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