Ammonia → HCID 71765591, compound

HRID 626830Notes

Reaction equation

HRID 626830 reaction equation
C([N:4]([CH2:8]C)C(C)C)(C)C.FC(F)(F)C(O)=O.[NH2:17][C:18]1[N:23]=[CH:22][N:21]=[C:20]2[N:24]([CH:28]([C:30]3[C:40]4[O:39][CH:38]([CH3:41])[CH2:37][N:36]([CH:42]5[CH2:45][CH:44]([C:46]([OH:48])=O)[CH2:43]5)[CH2:35][C:34]=4[C:33](F)=[C:32]([Cl:50])[CH:31]=3)[CH3:29])[N:25]=[C:26]([CH3:27])[C:19]=12.F[P-](F)(F)(F)(F)F.C[N+:59](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.N>CN(C)C=O.C(O)C>[NH2:17][C:18]1[N:23]=[CH:22][N:21]=[C:20]2[N:24]([CH:28]([C:30]3[C:40]4[O:39][C@@H:38]([CH3:41])[CH2:37][N:36]([CH:42]5[CH2:43][CH:44]([C:46]([NH2:59])=[O:48])[CH2:45]5)[CH2:35][C:34]=4[C:33]([C:8]#[N:4])=[C:32]([Cl:50])[CH:31]=3)[CH3:29])[N:25]=[C:26]([CH3:27])[C:19]=12

Participants

7

Reactant 4

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86697523HCID 86697523, compound

Product 1

HCID 71765591HCID 71765591, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

N,N-Diisopropylethylamine (78 μl, 0.45 mmol) was added to a mixture of 3-[9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-6-fluoro-2-methyl-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]cyclobutanecarboxylic acid trifluoroacetate (44 mg, 0.09 mmol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (34 mg, 0.09 mmol) in N,N-dimethylformamide (2 mL) at room temperature. A solution of ammonia in ethanol (2.0 M, 130 μl) was added and the reaction was stirred at room temperature for 1.5 hrs. The reactions were purified by prep HPLC on C-18 column eluting water:acetonitrile gradient buffered pH 10 to give two diastereomers: Peak #1 (Example 43): LCMS calculated for C23H28ClFN7O2 (M+H)+: m/z=488.2; found: 488.2; Peak #2 (Example 44): LCMS calculated for C23H28ClFN7O2 (M+H)+: m/z=488.2; found: 488.2.

Workup

  1. customThe reactions were purified by prep HPLC on C-18 column
  2. washeluting water
  3. customacetonitrile gradient buffered pH 10 to give two diastereomers

Sources & evidence

ORD record
ord-d10c814f94b24a6f99df539622080391
Source dataset
uspto-grants-2016_04
Patent number
US09309251B2

Reaction notes

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