Nitrogen → (2S)-Methyl 2-(7-(4-allyl-7-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 1400707Notes

Reaction equation

HRID 1400707 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:28]=[C:11]3[N:12]=[C:13]([CH3:27])[C:14]([C@H:17]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:18]([O:20][CH3:21])=[O:19])=[C:15](I)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:29]([N:32]1[CH2:37][CH2:36][O:35][C:34]2[CH:38]=[C:39]([CH3:51])[C:40](B3OC(C)(C)C(C)(C)O3)=[CH:41][C:33]1=2)[CH:30]=[CH2:31].C([O-])([O-])=O.[Na+].[Na+].N#N>CN(C=O)C.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>[CH2:29]([N:32]1[CH2:37][CH2:36][O:35][C:34]2[CH:38]=[C:39]([CH3:51])[C:40]([C:15]3[N:10]4[N:9]=[C:8]([C:4]5[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=5)[CH:28]=[C:11]4[N:12]=[C:13]([CH3:27])[C:14]=3[C@H:17]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:18]([O:20][CH3:21])=[O:19])=[CH:41][C:33]1=2)[CH:30]=[CH2:31]

Participants

7

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 86710746(S)-methyl 2-(2-(3-bromophenyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateHCID 867107574-Allyl-7-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine

Product 1

HCID 86710759(2S)-Methyl 2-(7-(4-allyl-7-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 25.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A solution of (S)-methyl 2-(2-(3-bromophenyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.100 g, 0.179 mmol), 4-allyl-7-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine (0.062 g, 0.197 mmol) and 2.0 M Na2CO3 (0.179 mL, 0.358 mmol) in dry DMF (3 mL) was sparged with N2 for 10 min, treated with Pd(Ph3P)4 (0.014 g, 0.013 mmol), sparged for 5 minutes, then heated (90° C.) for 48 h. The reaction was cooled, filtered (0.45 μm syringe tip filter) and purified by prep-HPLC to afford the desired product (0.028 g, 0.045 mmol, 25.2% yield) as a yellow oily film. 1H NMR (500 MHz, CDCl3) δ 7.99 (t, J=1.7 Hz, 1H), 7.78 (dt, J=7.7, 1.3 Hz, 1H), 7.49-7.42 (m, 1H), 7.26-7.22 (m, 1H), 6.87-6.80 (m, 2H), 6.61 (s, 1H), 5.86-5.73 (m, 1H), 5.22 (dd, J=17.2, 1.6 Hz, 1H), 5.17 (dd, J=10.2, 1.4 Hz, 1H), 5.11 (s, 1H), 4.42-4.30 (m, 2H), 3.87-3.78 (m, 1H), 3.75-3.68 (m, 1H), 3.66 (s, 3H), 3.42-3.34 (m, 1H), 3.32-3.24 (m, 1H), 2.76 (s, 3H), 1.90 (s, 3H), 1.17 (s, 9H). LCMS (M+H)=621.3.

Workup

  1. customsparged for 5 minutes
  2. temperatureThe reaction was cooled
  3. filtrationfiltered
  4. filtration(0.45 μm syringe tip filter)
  5. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-2e7cc6e44e084dafa3f38bce7cbffefe
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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