Hydrochloric Acid → 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

HRID 626820Notes

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](C(OC(C)(C)C)=O)[CH2:19][C:18]=4[C:17]([CH3:32])=[C:16]([Cl:33])[CH:15]=3)[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12.Cl.O=[C:36]1[CH2:39][N:38]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:37]1.C([BH3-])#N.[Na+]>O1CCOCC1>[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:36]5[CH2:37][N:38]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:39]5)[CH2:19][C:18]=4[C:17]([CH3:32])=[C:16]([Cl:33])[CH:15]=3)[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12

Participants

Conditions

Temperature: 60 °C

Procedure

tert-Butyl 9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-6-methyl-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (100 mg, 0.2 mmol) was treated with 4 N HCl in dioxane (1 mL), and then the solvent was evaporated. The residue was stirred in methanol (5 mL) and tert-butyl 3-oxoazetidine-1-carboxylate (140 mg, 0.84 mmol) was added. Sodium cyanoborohydride (120 mg, 1.9 mmol) was added and the mixture was warmed to 60° C. for 1.5 hours. Purification by preparative LCMS (pH 10) gave the desired compound (3.3 mg, 10%). LCMS calculated for C26H35ClN7O3 (M+H)+: m/z=528.2; found: 528.3. 1H NMR (300 MHz, CD3OD): δ 8.14 (s, 1 H), 7.33 (s, 1 H), 6.33 (m, 1 H), 4.00 (m, 2 H), 3.82 (m, 1 H), 3.74 (m, 2 H), 3.63 (m, 3 H), 3.41 (m, 1 H), 2.76 (m, 2 H), 2.58 (s, 3 H), 2.37 (s, 3 H), 1.79 (m, 3 H), 1.42 (s, 9H).

Workup

customthe solvent was evaporated
customPurification by preparative LCMS (pH 10)

Sources & evidence

ORD record: ord-4bf9d332c0d947468f4c38ff823028f0
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309251B2

Reaction notes

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