Lithium Hydroxide → HCID 60205665, compound

HRID 2203976Notes

Reaction equation

HRID 2203976 reaction equation
CCN(C(C)C)C(C)C.[CH3:10][O:11][C@H:12]([CH3:16])[C:13](O)=[O:14].C1N(P([Cl:31])(N2C(=O)OCC2)=O)C(=O)OC1.[NH2:32][C:33]1[C:41]2[C:36](=[N:37][CH:38]=[C:39]([Cl:56])[C:40]=2[N:42]2[CH2:47][CH2:46][CH2:45][C@@H:44]([NH:48]C(=O)OC(C)(C)C)[CH2:43]2)[NH:35][CH:34]=1.[Li+].[OH-]>CN1C(=O)CCC1.C(#N)C.O.C(Cl)Cl>[ClH:31].[NH2:48][C@@H:44]1[CH2:45][CH2:46][CH2:47][N:42]([C:40]2[C:39]([Cl:56])=[CH:38][N:37]=[C:36]3[NH:35][CH:34]=[C:33]([NH:32][C:13](=[O:14])[C@H:12]([O:11][CH3:10])[CH3:16])[C:41]=23)[CH2:43]1

Participants

10

Reactant 5

HCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 2733584(2R)-2-methoxypropanoic acidHCID 67045610(R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 60205665HCID 60205665, compoundYield 61.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

NMP (4 mL), DIEA (2.47 g, 19.1 mmol), (R)-2-methoxypropanoic acid (1.42 g, 13.7 mmol), and BOP-Cl (3.48 g, 13.7 mmol) were added to a solution of crude (R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (1.00 g, 2.73 mmol; Example 91, Step A) in NMP (3.3 mL). The reaction was stirred for 30 minutes. 3M LiOH (25 mL) was then added, and the reaction was stirred at room temperature for 18 hours. Water and DCM were added to the reaction mixture, and the layers were separated. The organic layer was dried, filtered, and concentrated. The resulting residue was purified by reverse phase chromatography (Biotage SP4, C-18 40M+, 5-95% water:ACN) to provide (R)—N-(4-((R)-3-aminopiperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-methoxypropanamide hydrochloride (655 mg, 56% yield) as a solid. 1H NMR (400 MHz, D2O) δ 8.03 (s, 1H), 7.50 (s, 1H), 3.99 (q, 1H), 3.58 (m, 1H), 3.46 (m, 1H), 3.37 (s, 3H), 3.29 (m, 1H), 3.15 (m, 1H), 3.00 (m, 1H), 2.09 (m, 1H), 1.80-1.60 (m, 2H), 1.51 (m, 1H), 1.34 (d, 3H). LCMS (APCI+) m/z 352.0 (M+H)+, Retention time=2.28 minutes (Method 3).

Workup

  1. stirringthe reaction was stirred at room temperature for 18 hours
  2. customthe layers were separated
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-95b6013c9b5c4eb491919f44f11dc717
Source dataset
uspto-grants-2016_06
Patent number
US09365568B2

Reaction notes

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