Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → [3-[4-(7-benzenesulfonyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-(4-chlorophenyl)-3-oxo-propyl]-carbamic acid tert-butyl ester

HRID 1192412Notes

Reaction equation

HRID 1192412 reaction equation
Cl.Cl.[C:3]1([S:9]([N:12]2[C:16]3[N:17]=[CH:18][N:19]=[C:20]([N:21]4[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]4)[C:15]=3[C:14]([CH3:27])=[CH:13]2)(=[O:11])=[O:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:28]([O:32][C:33]([NH:35][CH2:36][CH:37]([C:41]1[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=1)[C:38](O)=[O:39])=[O:34])([CH3:31])([CH3:30])[CH3:29].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:28]([O:32][C:33](=[O:34])[NH:35][CH2:36][CH:37]([C:41]1[CH:42]=[CH:43][C:44]([Cl:47])=[CH:45][CH:46]=1)[C:38]([N:24]1[CH2:25][CH2:26][N:21]([C:20]2[C:15]3[C:14]([CH3:27])=[CH:13][N:12]([S:9]([C:3]4[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=4)(=[O:10])=[O:11])[C:16]=3[N:17]=[CH:18][N:19]=2)[CH2:22][CH2:23]1)=[O:39])([CH3:31])([CH3:29])[CH3:30]

Participants

5

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 446078373-(((Tert-butoxy)carbonyl)amino)-2-(4-chlorophenyl)propanoic acidHCID 675377857-Benzenesulfonyl-5-methyl-4-piperazin-1-yl-7H-pyrrolo[2,3-d]pyrimidine dihydrochloride

Product 1

HCID 68406059[3-[4-(7-benzenesulfonyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-(4-chlorophenyl)-3-oxo-propyl]-carbamic acid tert-butyl esterYield 99.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The 7-benzenesulfonyl-5-methyl-4-piperazin-1-yl-7H-pyrrolo[2,3-d]pyrimidine bis-hydrochloride (200 mg, 0.465 mmol) and 3-tert-butoxycarbonylamino-2-(4-chlorophenyl)-propionic acid (146 mg, 0.488 mmol) were dissolved/suspended in 2.0 mL of DMF at room temperature and treated with TEA (259 μL, 1.86 mmol). The HBTU (194 mg, 0.511 mmol) was added in one sum, and the reaction was allowed to stir overnight at room temperature to completion. The reaction was partitioned between ethyl acetate and diluted NaHCO3 solution. The aqueous was extracted with ethyl acetate, and the organics were combined. The organic was washed with water, then brine, separated, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by chromatography (silica gel eluted with 70:30 ethyl acetate:hexanes) to afford the pure [3-[4-(7-benzenesulfonyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-(4-chlorophenyl)-3-oxo-propyl]-carbamic acid tert-butyl ester as colorless gel (295 mg, 99%). 1H NMR (CDCl3, 400 MHz) δ 8.44 (s, 1H), 8.16 (d, J=8.4 Hz, 2H), 7.59 (t, J=7.2 Hz, 1H), 7.49 (appt, J=7.6 Hz, 2H), 7.31 (m, 3H), 7.20 (d, J=8.0 Hz, 2H), 5.12 (m, 1H), 4.09 (m, 1H), 3.92 (m, 1H), 3.60 (m, 1H), 3.56-3.46 (m, 4H), 3.38 (d, J=10.4 Hz, 2H), 3.32 (m, 1H), 2.90 (m, 1H), 2.29 (s, 3H), 1.41 (s, 9H). LCMS (APCI+) m/z 639 [M+H]+; Rt=3.70 min.

Workup

  1. customThe reaction was partitioned between ethyl acetate and diluted NaHCO3 solution
  2. extractionThe aqueous was extracted with ethyl acetate
  3. washThe organic was washed with water
  4. custombrine, separated
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by chromatography (silica gel eluted with 70:30 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-acc1841d97e7414fab57bd1c6b3d04aa
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

Loading…