Dichloromethane → tert-butyl (S)-2-(4-(tert-butyl)benzamido)-3-(4-(5-(4-(heptyloxy)phenyl)-4-methoxypyrimidin-2-yl)phenyl)propanoate

HRID 1775848Notes

Reaction equation

HRID 1775848 reaction equation
Br[C:2]1[C:3]([O:36][CH3:37])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C@H:15]([NH:23][C:24](=[O:35])[C:25]3[CH:30]=[CH:29][C:28]([C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:27][CH:26]=3)[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:10][CH:9]=2)=[N:6][CH:7]=1.[CH2:38]([O:45][C:46]1[CH:51]=[CH:50][C:49](B(O)O)=[CH:48][CH:47]=1)[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44].C(=O)([O-])[O-].[Na+].[Na+].C(Cl)Cl>C(#N)C.C1COCC1.O.C([O-])(O)=O.[Na+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:31]([C:28]1[CH:29]=[CH:30][C:25]([C:24]([NH:23][C@@H:15]([CH2:14][C:11]2[CH:12]=[CH:13][C:8]([C:5]3[N:4]=[C:3]([O:36][CH3:37])[C:2]([C:49]4[CH:50]=[CH:51][C:46]([O:45][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44])=[CH:47][CH:48]=4)=[CH:7][N:6]=3)=[CH:9][CH:10]=2)[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:35])=[CH:26][CH:27]=1)([CH3:34])([CH3:33])[CH3:32]

Participants

10

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 43391844-Heptyloxyphenylboronic Acid (contains varying amounts of Anhydride)HCID 86689697tert-butyl (S)-3-(4-(5-bromo-4-methoxypyrimidin-2-yl)phenyl)-2-(4-(tert-butyl)benzamido)propanoate

Product 1

HCID 86689699tert-butyl (S)-2-(4-(tert-butyl)benzamido)-3-(4-(5-(4-(heptyloxy)phenyl)-4-methoxypyrimidin-2-yl)phenyl)propanoateYield 94.9%

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
110 °C

Procedure

Prepared using General Procedure 10: A mixture of tert-butyl (S)-3-(4-(5-bromo-4-methoxypyrimidin-2-yl)phenyl)-2-(4-(tert-butyl)benzamido)propanoate (18.0 mg, 0.031 mmol), (4-(heptyloxy)phenyl)boronic acid (10.0 mg, 0.042 mmol) and sodium carbonate (8.97 mg, 0.084 mmol) in acetonitrile (0.80 mL), THF (0.80 mL) and H2O (0.40 mL) was degassed for 10 min. Pd(dppf)Cl2:CH2Cl2 (3.09 mg, 0.003 mmol) was added and the reaction mixture heated at 110° C. in a microwave for 30 min. Once cooled, the reaction was diluted with NaHCO3 (5 mL) and extracted with EA (3×5 mL). The combined organics were dried over MgSO4 and concentrated. The residue was purified by column chromatography (EA:hexanes) to afford 20.0 mg (60%) of tert-butyl (S)-2-(4-(tert-butyl)benzamido)-3-(4-(5-(4-(heptyloxy)phenyl)-4-methoxypyrimidin-2-yl)phenyl)propanoate as pale yellow solid. LCMS-ESI (m/z) calculated for C42H53N3O5: 679.8; no ion observed, tR=13.83 min. (Method 2).

Workup

  1. customPrepared
  2. customwas degassed for 10 min
  3. temperatureOnce cooled
  4. extractionextracted with EA (3×5 mL)
  5. dry with materialThe combined organics were dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (EA:hexanes)

Sources & evidence

ORD record
ord-7f7e7786f3a7498480db9f1b21f905c3
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

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