Water → HCID 86658346, compound

HRID 340104Notes

Reaction equation

HRID 340104 reaction equation
Cl[C:2]1[C:3]2[C@H:10]([CH3:11])[CH2:9][CH2:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Br-].[CH2:13]([O:15][C:16]([C:18]1[S:22][C:21]([Zn+])=[CH:20][CH:19]=1)=[O:17])[CH3:14].C1COCC1.O>C(OCC)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:11][C@H:10]1[C:3]2[C:2]([C:21]3[S:22][C:18]([C:16]([O:15][CH2:13][CH3:14])=[O:17])=[CH:19][CH:20]=3)=[N:7][CH:6]=[N:5][C:4]=2[CH2:8][CH2:9]1

Participants

7

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 59670769(R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidineHCID 178469119HCID 178469119, compound

Product 1

HCID 86658346HCID 86658346, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
70 °C

Procedure

Pd(PPh3)4 (10 mg, 0.09 mmol) was added to a degassed solution of (R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta-[d]-pyrimidine (300 mg, 1.78 mmol) and a 0.5M solution of 5-ethoxycarbonyl-2-thienylzinc bromide in THF (3.6 mL, 1.78 mmol). The reaction mixture was stirred at 70° C. for 16 hours and then it was cooled to room temperature and diluted with diethyl ether (10 mL). Water was added (5 mL) and a precipitate was formed and filtered. The solid was washed with more diethyl ether and the filtrate was concentrated. The resulting oil was purified on silica gel (0%-75% EtOAc/hexanes) to yield (R)-ethyl 5-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)thiophene-2-carboxylate as an oil (400 mg, 78%). m/z: 289 (MH+), 1H NMR (CDCl3): δ (ppm) 8.95 (s, 1H), 7.84-7.82 (m, 1H), 7.70-7.69 (m 1H), 4.39 (dq, 2H, J1=7.2 Hz, J2=1.2 Hz), 3.77 (quint., 1H, J=7.2 Hz), 3.23-1.14 (m, 1H), 3.001-2.95 (m, 1H), 2.42-2.31 (m, 1H), 1.98-1.92 (m, 1H), 1.40 (dt, 3H, J1=7.2 Hz, J2=1.2 Hz), 1.29 (d, 3H, J=7.2 Hz).

Workup

  1. temperatureit was cooled to room temperature
  2. customa precipitate was formed
  3. filtrationfiltered
  4. washThe solid was washed with more diethyl ether
  5. concentrationthe filtrate was concentrated
  6. customThe resulting oil was purified on silica gel (0%-75% EtOAc/hexanes)

Sources & evidence

ORD record
ord-fee34e46fe1b45f88f3713cebf12c39b
Source dataset
uspto-grants-2014_11
Patent number
US08895566B2

Reaction notes

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