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

HRID 1400708Notes

Reaction equation

HRID 1400708 reaction equation
[CH2:1]([N:4]1[CH2:9][CH2:8][O:7][C:6]2[CH:10]=[C:11]([CH3:41])[C:12]([C:14]3[N:19]4[N:20]=[C:21]([C:23]5[CH:28]=[CH:27][CH:26]=[C:25](Br)[CH:24]=5)[CH:22]=[C:18]4[N:17]=[C:16]([CH3:30])[C:15]=3[C@H:31]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[C:32]([O:34][CH3:35])=[O:33])=[CH:13][C:5]1=2)[CH:2]=[CH2:3].[CH2:42]([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=1B(O)O)[CH2:43][CH:44]=[CH2:45].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>[CH2:1]([N:4]1[CH2:9][CH2:8][O:7][C:6]2[CH:10]=[C:11]([CH3:41])[C:12]([C:14]3[N:19]4[N:20]=[C:21]([C:23]5[CH:24]=[C:25]([C:47]6[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=6[CH2:42][CH2:43][CH:44]=[CH2:45])[CH:26]=[CH:27][CH:28]=5)[CH:22]=[C:18]4[N:17]=[C:16]([CH3:30])[C:15]=3[C@H:31]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[C:32]([O:34][CH3:35])=[O:33])=[CH:13][C:5]1=2)[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 86710753(2-(But-3-en-1-yl)phenyl)boronic acidHCID 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)acetate

Product 1

HCID 86710760(2S)-Methyl 2-(7-(4-allyl-7-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(2'-(but-3-en-1-yl)-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A solution of (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 (0.028 g, 0.045 mmol), (2-(but-3-en-1-yl)phenyl)boronic acid (0.016 g, 0.090 mmol) and 2.0 M aq. Na2CO3 (0.056 ml, 0.113 mmol) in dry DMF (2.5 ml) was sparged with N2 for 15 min, then treated with Pd(Ph3P)4 (3.7 mg, 3.2 μmol), sparged for another 5 min, then heated (90° C.) for 16 h. The reaction was cooled, filtered (0.45 μm syringe tip filter), and purified by prep-HPLC to afford the desired product. 1H NMR (500 MHz, CDCl3) δ 7.88 (dt, J=7.9, 1.3 Hz, 1H), 7.83 (t, J=1.5 Hz, 1H), 7.44 (t, J=7.6 Hz, 1H), 7.32-7.36 (m, 2H), 7.29-7.31 (m, 1H), 7.26-7.28 (m, 2H), 6.88 (s, 1H), 6.81 (s, 1H), 6.64 (s, 1H), 5.65-5.85 (m, 2H), 5.21 (dd, J=17.2, 1.6 Hz, 1H), 5.10-5.15 (m, 2H), 4.85-4.94 (m, 2H), 4.33-4.38 (m, 2H), 3.78-3.86 (m, 1H), 3.68-3.76 (m, 1H), 3.67 (s, 3H), 3.23-3.40 (m, 2H), 2.78 (s, 3H), 2.66-2.74 (m, 2H), 2.26 (td, J=7.9, 6.7 Hz, 2H), 1.92 (s, 3H), 1.20 (s, 9H). LCMS (M+H)=671.5.

Workup

  1. customsparged for another 5 min
  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-44c74998e4b84eb484c3627cda1ee979
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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