Sodium Carbonate → HCID 72721745, compound

HRID 874743Notes

Reaction equation

HRID 874743 reaction equation
[CH:1]1([C@@H:6]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[NH:7][C:8]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[NH:15][N:14]=[C:13]3I)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.CC1(C)C(C)(C)OB([C:34]2[CH:39]=[CH:38][C:37]([N:40]3[CH2:46][C:42]4([CH2:45][O:44][CH2:43]4)[CH2:41]3)=[CH:36][CH:35]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:45]1[C:42]2([CH2:46][N:40]([C:37]3[CH:38]=[CH:39][C:34]([C:13]4[C:12]5[C:16](=[CH:17][CH:18]=[C:10]([C:8]([NH:7][C@@H:6]([CH:1]6[CH2:5][CH2:4][CH2:3][CH2:2]6)[C:20]6[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=6)=[O:9])[CH:11]=5)[NH:15][N:14]=4)=[CH:35][CH:36]=3)[CH2:41]2)[CH2:43][O:44]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 86706886HCID 86706886, compoundHCID 178523848HCID 178523848, compound

Product 1

HCID 72721745HCID 72721745, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
130 °C

Procedure

The title compound was synthesized according to General Method C2 by utilizing (S)—N-(cyclopentyl(pyridin-2-yl)methyl)-3-iodo-1H-indazole-5-carboxamide (135 mg, 0.30 mmol), 6-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-oxa-6-azaspiro[3.3]heptane (100 mg, 0.33 mmol), Pd(PPh3)4 (36 mg, 0.044 mmol) and 2 M aq Na2CO3 (0.3 mL) in PhMe/EtOH (14 mL, 1:1 mixture). The reaction mixture was heated under microwave irradiation at 130° C. for 3 h. The reaction mixture was diluted with EtOAc (20 mL) and washed with H2O (20 mL), dried (MgSO4) and concentrated under vacuum to give a crude product. Purification by flash chromatography (Biotage Isolera, 50 g HP-SIL, 60-100% EtOAc in hexanes then 0-20% DCM in MeOH) gave the product as a yellow solid. Further purification using reverse phase chromatography (Biotage Isolera, 50 g C18, 10-90% MeCN in H2O) followed by trituration with MeOH gave the title compound as a pale yellow solid (34 mg, 23%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.18 (s, 1H), 8.88 (d, J=8.3 Hz, 1H), 8.34-8.63 (m, 2H), 7.80-7.93 (m, 3H), 7.75 (t, J=6.9 Hz, 1H), 7.54 (d, J=8.5 Hz, 1H), 7.47 (d, J=8.0 Hz, 1H), 7.24 (t, J=5.3 Hz, 1H), 6.60 (d, J=8.5 Hz, 2H), 4.92 (t, J=9.0 Hz, 1H), 4.74 (s, 4H), 4.05 (s, 4H), 2.53-2.62 (m, 1H), 1.87 (s, 1H), 1.35-1.70 (m, 5H), 1.15-1.35 (m, 2H); MS ESI 494.4 [M+H]+, calcd for [C30H31N5O2+H]+ 494.3.

Workup

  1. washwashed with H2O (20 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated under vacuum
  4. customto give a crude product

Sources & evidence

ORD record
ord-ec786b667559473db49de4b045a09a76
Source dataset
uspto-grants-2015_03
Patent number
US08980934B2

Reaction notes

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