Lithium Hydroxide → (2S)-2-Boc-aminomethyl-3-(4-chlorophenyl)-1-[4-(5-thiophen-2-yl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pip-erazin-1-yl]-propan-1-one

HRID 1192361Notes

Reaction equation

HRID 1192361 reaction equation
Cl.Cl.C1(S([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]([C:27]3[S:28][CH:29]=[CH:30][CH:31]=3)=[CH:13]2)(=O)=O)C=CC=CC=1.CCN([CH:38]([CH3:40])[CH3:39])C(C)C.C([CH:48]([NH2:61])[C@H:49]([CH2:53][C:54]1[CH:59]=[CH:58][C:57]([Cl:60])=[CH:56][CH:55]=1)[C:50]([OH:52])=[O:51])(OC(C)(C)C)=O.CN([C:65]([O:69]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Li+].[OH-].[C:88]([O-])(O)=O.[Na+]>C(Cl)Cl.CO>[C:50]([C@:49]([CH2:48][NH2:61])([CH2:53][C:54]1[CH:55]=[CH:56][C:57]([Cl:60])=[CH:58][CH:59]=1)[C:65]([N:24]1[CH2:23][CH2:22][N:21]([C:20]2[C:15]3[C:14]([C:27]4[S:28][CH:29]=[CH:30][CH:31]=4)=[CH:13][NH:12][C:16]=3[N:17]=[CH:18][N:19]=2)[CH2:26][CH2:25]1)=[O:69])([O:52][C:38]([CH3:40])([CH3:88])[CH3:39])=[O:51]

Participants

9

Reactant 6

HCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 675387477-Benzenesulfonyl-4-piperazin-1-yl-5-thiophen-2-yl-7H-pyrrolo[2,3-d]pyrimidine dihydrochlorideHCID 67539705(2s)-2-(Boc-aminomethyl)-3-(4-chlorophenyl)-propionic acid

Product 1

HCID 86598733(2S)-2-Boc-aminomethyl-3-(4-chlorophenyl)-1-[4-(5-thiophen-2-yl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pip-erazin-1-yl]-propan-1-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 7-Benzenesulfonyl-4-piperazin-1-yl-5-thiophen-2-yl-7H-pyrrolo[2,3-d]pyrimidine dihydrochloride (50 mg, 0.10 mmol), DIEA (0.10 mL, 0.60 mmol), and (2S)-2-(Boc-aminomethyl)-3-(4-chlorophenyl)-propionic acid (38 mg, 0.12 mmol) in 2 mL DCM was added HBTU (44 mg, 0.12 mmol). The reaction mixture was stirred at room temperature 2 hours, after which 2 mL MeOH and 0.5 mL 3M LiOH were added. The reaction mixture was heated to 35° C. and stirred 2 hours, after which saturated NaHCO3 was added, and the mixture was extracted with DCM. The combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was purified on silica gel (flushed with 2:1 DCM:EtOAc, then gradient to 1:4 DCM:EtOAc) to give (2S)-2-Boc-aminomethyl-3-(4-chlorophenyl)-1-[4-(5-thiophen-2-yl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pip-erazin-1-yl]-propan-1-one, which was used in the next step.

Workup

  1. temperatureThe reaction mixture was heated to 35° C.
  2. stirringstirred 2 hours
  3. extractionthe mixture was extracted with DCM
  4. dry with materialThe combined extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude was purified on silica gel (
  8. customflushed with 2:1 DCM

Sources & evidence

ORD record
ord-3ba1dc7d18354748928301605e50ad77
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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