Triethylamine → 9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-4-[1-(2-hydroxyethyl)azetidin-3-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepine-6-carbonitrile

HRID 626847Notes

Reaction equation

HRID 626847 reaction equation
Cl.Cl.Cl.[NH2:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]2[N:11]([CH:15]([C:17]3[CH:18]=[C:19]([Cl:34])[C:20]([C:32]#[N:33])=[C:21]4[C:27]=3[O:26][CH2:25][CH2:24][N:23]([CH:28]3[CH2:31][NH:30][CH2:29]3)[CH2:22]4)[CH3:16])[N:12]=[C:13]([CH3:14])[C:6]=12.Br[CH2:36][CH2:37][OH:38].C(N(CC)CC)C>CN(C)C=O>[NH2:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]2[N:11]([CH:15]([C:17]3[CH:18]=[C:19]([Cl:34])[C:20]([C:32]#[N:33])=[C:21]4[C:27]=3[O:26][CH2:25][CH2:24][N:23]([CH:28]3[CH2:31][N:30]([CH2:36][CH2:37][OH:38])[CH2:29]3)[CH2:22]4)[CH3:16])[N:12]=[C:13]([CH3:14])[C:6]=12

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 108982-BromoethanolHCID 86697539HCID 86697539, compound

Product 1

HCID 717655559-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-4-[1-(2-hydroxyethyl)azetidin-3-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepine-6-carbonitrileYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

9-[1-(4-Amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-4-azetidin-3-yl-7-chloro-2,3,4,5-tetrahydro-1,4-benzoxazepine-6-carbonitrile (0.015 g, 0.034 mmol) (from Example 46, Step 15) and 2-bromoethanol (0.0097 mL, 0.14 mmol) were combined in N,N-dimethylformamide (1 mL) with triethylamine (0.019 mL, 0.14 mmol) at room temperature. The reaction was heated to 85° C. and after heating for 2 hrs the reaction was concentrated in vacuo and the residue was purified by prep HPLC on a C-18 column eluting water:acetonitrile gradient buffered pH 10 to give the desired compound as a white amorphous solid (0.008 g, 50%). LCMS calculated for C23H28ClN8O2 (M+H)+: m/z=483.2; found: 483.2.

Workup

  1. temperatureafter heating for 2 hrs the reaction
  2. concentrationwas concentrated in vacuo
  3. customthe residue was purified by prep HPLC on a C-18 column
  4. washeluting water

Sources & evidence

ORD record
ord-fc5ae508e22c4ceb81dbf9bebceb3afd
Source dataset
uspto-grants-2016_04
Patent number
US09309251B2

Reaction notes

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