Nitrogen → (2S)-2-(tert-Butoxy)-2-[(22S)-5-ethenyl-17-fluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetic acid

HRID 1482078Notes

Reaction equation

HRID 1482078 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C[O:31][C:32](=[O:83])[C@@H:33]([O:78][C:79]([CH3:82])([CH3:81])[CH3:80])[C:34]1[C:63]([CH3:64])=[C:62]([C:65]2C=CN=C[CH:66]=2)[C:61]2=[N:71][C:58]3=[CH:59][N:60]2[C:35]=1[N:36]1[CH2:76][CH2:75][C:39]([CH3:77])([O:40][CH2:41][CH2:42][CH2:43][CH2:44][C@H:45]([CH3:74])[O:46][C:47]2[CH:48]=[CH:49][C:50]([F:73])=[CH:51][C:52]=2[C:53]2[CH:72]=[C:57]3[CH:56]=[CH:55][CH:54]=2)[CH2:38][CH2:37]1.CN1CC(=O)OB(C2C=CN=CC=2)OC(=O)C1.BrC1C2=NC3=CN2C(N2CCC(C)(OCCCC[C@H](C)OC4C=CC(F)=CC=4C4C=C3C=CC=4)CC2)=C([C@H](OC(C)(C)C)C(OC)=O)C=1C.N#N.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].O1CCOCC1>[C:79]([O:78][C@@H:33]([C:34]1[C:63]([CH3:64])=[C:62]([CH:65]=[CH2:66])[C:61]2=[N:71][C:58]3=[CH:59][N:60]2[C:35]=1[N:36]1[CH2:37][CH2:38][C:39]([CH3:77])([O:40][CH2:41][CH2:42][CH2:43][CH2:44][C@H:45]([CH3:74])[O:46][C:47]2[CH:48]=[CH:49][C:50]([F:73])=[CH:51][C:52]=2[C:53]2[CH:72]=[C:57]3[CH:56]=[CH:55][CH:54]=2)[CH2:75][CH2:76]1)[C:32]([OH:83])=[O:31])([CH3:80])([CH3:81])[CH3:82]

Participants

8

Reactant 5

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 713105736-Methyl-2-(pyridin-4-yl)-1,3,6,2-dioxazaborocane-4,8-dioneHCID 118316311Methyl(2S)-2-[(22S)-5-bromo-17-fluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2, 4, 6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]-2-(tert-butoxy)acetateHCID 131736667Methyl(2S)-2-(tert-butoxy)-2-[(22S)-17-fluoro-4,22,28-trimethyl-5-(pyridin-4-yl)-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate 2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

Product 1

HCID 118316324(2S)-2-(tert-Butoxy)-2-[(22S)-5-ethenyl-17-fluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetic acid

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Methyl(2S)-2-(tert-butoxy)-2-[(22S)-17-fluoro-4,22,28-trimethyl-5-(pyridin-4-yl)-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate 2-Dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (1.672 mg, 4.07 μmol, 0.2 equiv), Pd(OAc)2 (0.457 mg, 2.036 μmol, 0.1 equiv), 6-methyl-2-(pyridin-4-yl)-1,3,6,2-dioxazaborocane-4,8-dione (5.72 mg, 0.024 mmol, 1.2 equiv) and methyl(2S)-2-[(22S)-5-bromo-17-fluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]-2-(tert-butoxy)acetate (15 mg, 0.020 mmol, 1.0 equiv) were mixed in a one drum vial with a stir bar. The vial was vacuumed and back filled with N2 triple times. Then to this mixture was added dioxane (339 μl) and potassium phosphate tribasic (76 μl, 0.153 mmol, 7.5 equiv). The resulted solution was degassed by N2 for 5 mins. Then it was stirred at 80° C. for 1.5 hours. It was diluted by EA and washed by NaHCO3. concentrated, to afford the pure enough product. LCMS (ESI, M+1): 735.4.

Workup

  1. customThe resulted solution was degassed by N2 for 5 mins
  2. additionIt was diluted by EA
  3. washwashed by NaHCO3
  4. concentrationconcentrated
  5. customto afford the pure enough product

Sources & evidence

ORD record
ord-52af0e217d88434ca76ae5c753b3f229
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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