Trifluoroacetic acid → (1R,2S)-2-(3-((E)-2-(2,3,4,5-tetrahydrobenzo[f][1,4]oxazepin-7-yl) vinyl)-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-one 2,2,2-trifluoroacetate

HRID 447553Notes

Reaction equation

HRID 447553 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C@H:11]3[C@@:13]4([C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[NH:15][C:14]4=[O:22])[CH2:12]3)=[CH:8][CH:9]=2)[NH:4][N:3]=1.CC1(C)C(C)(C)OB(/[CH:31]=[CH:32]/[C:33]2[CH:34]=[CH:35][C:36]3[O:42][CH2:41][CH2:40][N:39](C(OC(C)(C)C)=O)[CH2:38][C:37]=3[CH:50]=2)O1.[C:52]([OH:58])([C:54]([F:57])([F:56])[F:55])=[O:53]>C(Cl)Cl>[F:55][C:54]([F:57])([F:56])[C:52]([OH:58])=[O:53].[O:42]1[C:36]2[CH:35]=[CH:34][C:33](/[CH:32]=[CH:31]/[C:2]3[C:10]4[C:5](=[CH:6][C:7]([C@H:11]5[C@@:13]6([C:21]7[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=7)[NH:15][C:14]6=[O:22])[CH2:12]5)=[CH:8][CH:9]=4)[NH:4][N:3]=3)=[CH:50][C:37]=2[CH2:38][NH:39][CH2:40][CH2:41]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 66734356(E)-tert-butyl 7-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)-2,3-dihydrobenzo[f][1,4]oxazepine-4(5H)-carboxylateHCID 178517040(1R*,2S*)-2-(3-iodo-1H-indazol-6-yl)-spiro[cyclopropane-1,3'-indolin]-2'-one

Product 1

HCID 67448884(1R,2S)-2-(3-((E)-2-(2,3,4,5-tetrahydrobenzo[f][1,4]oxazepin-7-yl) vinyl)-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-one 2,2,2-trifluoroacetateYield 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The title compound was synthesized according to the method of Example A51B, by using (1R,2S)-2-(3-iodo-1H-indazol-6-yl)spiro[cyclopropane-1,3′-indolin]-2′-one (105 mg, 0.27 mmol) and (E)-tert-butyl 7-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)-2,3-dihydrobenzo[f][1,4]oxazepine-4(5H)-carboxylate (130 mg, 0.32 mmol). The residue from the reaction was dissolved into CH2Cl2 (5 mL) and TFA (0.2 mL) was added and the mixture was stirred for 1 h and concentrated to dryness. Purification by preparative HPLC gave the title compound as a cream solid (40 mg, 30%). 1H NMR (400 MHz, CD3OD) δ 7.97 (d, J=8.2 Hz, 1H), 7.68-7.64 (m, 2H), 7.50-7.39 (m, 3H), 7.16 (d, J=8.2 Hz, 1H), 7.07-7.01 (m, 2H), 6.94 (d, J=7.8 Hz, 1H), 6.57 (t, J=7.6 Hz, 1H), 5.98 (d, J=7.4 Hz, 1H), 4.45 (s, 2H), 4.39 (br. s, 2H), 3.68 (br. s, 2H), 3.39-3.33 (m, 1H) 2.25-2.16 (m, 2H); MS ESI 449.3 [M+H]+, calcd for [C28H24N4O2+H]+ 449.2.

Workup

  1. customThe title compound was synthesized
  2. additionwas added
  3. concentrationconcentrated to dryness
  4. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-c34b6cd632844aad941d6e727ce85b7c
Source dataset
uspto-grants-2013_07
Patent number
US08481525B2

Reaction notes

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