Diisopropylethylamine → HCID 118078118, compound

HRID 1482778Notes

Reaction equation

HRID 1482778 reaction equation
I[C:2]1[C:7]([C@H:8]([CH3:14])[CH2:9][C:10]([O:12][CH3:13])=[O:11])=[C:6]([I:15])[N:5]=[CH:4][N:3]=1.[C:16]([N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1)([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].C(N(CC)C(C)C)(C)C>CO>[I:15][C:6]1[N:5]=[CH:4][N:3]=[C:2]([N:26]2[CH2:25][CH2:24][N:23]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:28][CH2:27]2)[C:7]=1[C@@H:8]([CH2:9][C:10]([O:12][CH3:13])=[O:11])[CH3:14]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 89907651HCID 89907651, compound

Product 1

HCID 118078118HCID 118078118, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

Into a solution of (R)-methyl 3-(4,6-diiodopyrimidin-5-yl)butanoate (212 g, 491 mmol) and Boc-piperazine (101 g, 540 mmol) in methanol (424 mL) was added N,N-diisopropylethylamine (94.3 mL, 540 mmol). The mixture was heated at 60° C. for 24 h. Methanol was distilled off under reduced pressure below 40° C. To the mixture was added 318 mL of tetrahydrofuran. The above solvent swap process was repeated twice. To the mixture were added 424 mL of tetrahydrofuran, 212 mL of saturated aqueous ammonium chloride, and 21.2 mL of water. The organic layer was washed with 212 mL (1.00 vol.) of saturated aqueous ammonium chloride. This tetrahydrofuran solution was used for next step without further purification (91% weight assay yield). 1H NMR (300 MHz, CDCl3) δ 8.25 (s, 1H), 3.80-3.67 (m, 1H), 3.65 (s, 3H), 3.60-3.56 (m, 4H), 3.21-3.18 (m, 4H), 3.14 (dd, J=16.2, 9.0 Hz, 1H), 2.81 (dd, J=16.2, 5.7 Hz, 1H), 1.48 (s, 9H), 1.47 (d, J=7.2 Hz, 3H). HRMS calcd. For C18H28IN4O4 [M+H]+: 491.1150. found 491.1154.

Workup

  1. distillationMethanol was distilled off under reduced pressure below 40° C
  2. additionTo the mixture was added 318 mL of tetrahydrofuran
  3. additionTo the mixture were added 424 mL of tetrahydrofuran, 212 mL of saturated aqueous ammonium chloride, and 21.2 mL of water
  4. washThe organic layer was washed with 212 mL (1.00 vol.) of saturated aqueous ammonium chloride
  5. customThis tetrahydrofuran solution was used for next step without further purification (91% weight assay yield)

Sources & evidence

ORD record
ord-5f805d21be214f268c4efe579b011f2f
Source dataset
uspto-grants-2016_08
Patent number
US09416110B2

Reaction notes

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