Ammonia → HCID 86677794, compound

HRID 1499869Notes

Reaction equation

HRID 1499869 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=O.FC(F)(F)C(O)=O.[NH2:15][C:16]1[N:21]=[CH:20][N:19]=[C:18]2[N:22]([CH:26]([C:28]3[C:29](OCC)=[C:30]([CH:37]4[CH2:40][N:39]([C:41]([CH3:46])([CH3:45])[C:42]([OH:44])=O)[CH2:38]4)[C:31]([C:35]#[N:36])=[C:32]([Cl:34])[CH:33]=3)[CH3:27])[N:23]=[C:24]([CH3:25])[C:17]=12.N.C(O)C.C([N:56](CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[NH2:15][C:16]1[N:21]=[CH:20][N:19]=[C:18]2[N:22]([CH:26]([C:28]3[C:29]([O:5][CH2:3][CH3:2])=[C:30]([CH:37]4[CH2:38][N:39]([C:41]([CH3:45])([CH3:46])[C:42]([NH2:56])=[O:44])[CH2:40]4)[C:31]([C:35]#[N:36])=[C:32]([Cl:34])[CH:33]=3)[CH3:27])[N:23]=[C:24]([CH3:25])[C:17]=12

Participants

7

Reactant 5

HCID 222AmmoniaHCID 702EthanolHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 86677791HCID 86677791, compound2×

Product 1

HCID 86677794HCID 86677794, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(3-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-6-cyano-2-ethoxyphenyl}azetidin-1-yl)-2-methylpropanoic acid bis(trifluoroacetate) (0.05 g, 0.069 mmol, chiral intermediate from Example 237, Step 1) and 2.0 M ammonia in ethanol (0.17 mL, 0.34 mmol) in N,N-dimethylformamide (1 mL) was treated with triethylamine (0.048 mL, 0.35 mmol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (0.046 g, 0.10 mmol) and stirred at room temperature for 1 h. The reaction mixture was quenched with a few drops of water, diluted with methanol, and purified by preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (25 mg, 73%). The product was isolated as a single enantiomer. 1H NMR (400 MHz, DMSO-d6) S 8.11 (s, 1H), 7.51 (s, 1H), 7.23 (s, 1H), 6.98 (s, 1H), 6.23 (q, J=7.0 Hz, 1H), 4.09-3.96 (m, 1H), 3.84-3.61 (m, 4H), 3.39-3.34 (m, 1H), 3.32-3.28 (m, 1H), 2.54 (s, 3H), 1.71 (d, J=7.0 Hz, 3H), 1.31 (t, J=6.9 Hz, 3H), 1.02 (s, 6H). LCMS for C24H30ClN8O2 (M+H)+: m/z=497.2; Found: 497.3.

Workup

  1. customThe reaction mixture was quenched with a few drops of water
  2. additiondiluted with methanol
  3. custompurified by preparative LCMS (XBridge C18 column
  4. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-c99069c39ac74ea3a8e9503343877543
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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