Triethylamine → HCID 71510233, compound

HRID 1499818Notes

Reaction equation

HRID 1499818 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[C:15]([O:31][CH3:32])=[C:16]([CH:22]4[CH2:25][N:24]([C@H:26]([CH3:30])[C:27]([OH:29])=O)[CH2:23]4)[C:17]([CH3:21])=[C:18]([Cl:20])[CH:19]=3)[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)[N:51]([CH3:53])[CH3:52])C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.CNC>CN(C=O)C.CO>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[C:15]([O:31][CH3:32])=[C:16]([CH:22]4[CH2:25][N:24]([C@H:26]([CH3:30])[C:27]([N:51]([CH3:53])[CH3:52])=[O:29])[CH2:23]4)[C:17]([CH3:21])=[C:18]([Cl:20])[CH:19]=3)[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 86677741HCID 86677741, compound

Product 1

HCID 71510233HCID 71510233, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (2R)-2-(3-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}azetidin-1-yl)propanoic acid (4 mg, 0.009 mmol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (4 mg, 0.009 mmol) in DMF (0.3 mL) at room temperature was added triethylamine (4 μL, 0.03 mmol) and dimethylamine hydrochloride (0.9 mg, 0.01 mmol). The reaction mixture was stirred for 1 h, then diluted with methanol and purified by preparative RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (2.7 mg, 63%). The product was isolated as a single diastereomer. LCMS calculated for C24H33ClN7O2 (M+H)+: m/z=486.2; Found: 486.1. 1H NMR (300 MHz, DMSO-d6): δ□ 8.09 (s, 1H), 7.23 (s, 1H), 6.18 (m, 1H), 3.78 (m, 3H), 3.50 (s, 3H), 3.01 (s, 3H), 3.0-2.9 (m, 3H), 2.77 (s, 3H), 2.54 (s, 3H), 2.06 (s, 3H), 1.67 (d, 3H), 0.98 (d, 3H) ppm.

Workup

  1. custompurified by preparative RP-HPLC (XBridge C18 column
  2. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-39c80cfe990140f8a51ddede597180c9
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

Loading…