Hydrochloric Acid → 1-{1-[4-(1-Acetylazetidin-3-yl)-7-chloro-6-methyl-2,3,4,5-tetrahydro-1,4-benzoxazepin-9-yl]ethyl}-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 626821Notes

Reaction equation

HRID 626821 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[C:24]4[O:23][CH2:22][CH2:21][N:20]([CH:25]5[CH2:28][N:27]([C:29](OC(C)(C)C)=[O:30])[CH2:26]5)[CH2:19][C:18]=4[C:17]([CH3:36])=[C:16]([Cl:37])[CH:15]=3)[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12.Cl.[CH:39](N(CC)C(C)C)(C)C.C(OC(=O)C)(=O)C>O1CCOCC1.CN(C)C=O.CO>[C:29]([N:27]1[CH2:26][CH:25]([N:20]2[CH2:19][C:18]3[C:17]([CH3:36])=[C:16]([Cl:37])[CH:15]=[C:14]([CH:12]([N:8]4[C:4]5=[N:5][CH:6]=[N:7][C:2]([NH2:1])=[C:3]5[C:10]([CH3:11])=[N:9]4)[CH3:13])[C:24]=3[O:23][CH2:22][CH2:21]2)[CH2:28]1)(=[O:30])[CH3:39]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 71739337tert-Butyl 3-[9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-6-methyl-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]azetidine-1-carboxylate

Product 1

HCID 717654001-{1-[4-(1-Acetylazetidin-3-yl)-7-chloro-6-methyl-2,3,4,5-tetrahydro-1,4-benzoxazepin-9-yl]ethyl}-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 13.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

tert-Butyl 3-[9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-6-methyl-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]azetidine-1-carboxylate (15 mg, 0.035 mmol) was treated with 4 N HCl in dioxane (1 mL), and then the solvent was evaporated. The residue was stirred in N,N-dimethylformamide (0.5 mL) with N,N-diisopropylethylamine (10 μL, 0.06 mmol) and acetic anhydride (20 μL, 0.2 mmol) was added. The mixture was stirred for 5 minutes and diluted with methanol. Purification by preparative LCMS (pH 10) gave the desired compound (2.2 mg, 13%). LCMS calculated for C23H29ClN7O2 (M+H)+: m/z=470.2; found: 470.2. 1H NMR (300 MHz, CD3OD): δ 8.14 (s, 1 H), 7.33 (s, 1 H), 6.33 (m, 1 H), 4.27 (m, 1 H), 4.02 (m, 2 H), 3.80 (m, 1 H), 3.72 (m, 1 H), 3.69 (m, 3 H), 3.48 (m, 1 H), 2.79 (m, 2 H), 2.58 (s, 3 H), 2.38 (s, 3 H), 1.82 (m, 3 H), 1.77 (m, 3 H).

Workup

  1. customthe solvent was evaporated
  2. additionwas added
  3. customPurification by preparative LCMS (pH 10)

Sources & evidence

ORD record
ord-47114057b62b43dfbc00bfc3779016bf
Source dataset
uspto-grants-2016_04
Patent number
US09309251B2

Reaction notes

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