Diisopropylethylamine → ethyl 3-[4-(tributylstannanyl)-1H-1,2,3-triazol-1-yl]propyl (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

HRID 2279896Notes

Reaction equation

HRID 2279896 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C:8](=[O:11])[NH:9][CH3:10])[C:5]([NH:12][C:13]2[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:36]=[CH:35][C:27]([CH2:28][P:29](=[O:34])([OH:33])[O:30][CH2:31][CH3:32])=[CH:26][C:25]=3[O:37][CH3:38])[N:14]=2)=[CH:4][CH:3]=1.[CH2:39]([Sn:43]([CH2:57][CH2:58][CH2:59][CH3:60])([CH2:53][CH2:54][CH2:55][CH3:56])[C:44]1[N:45]=[N:46][N:47]([CH2:49][CH2:50][CH2:51]O)[CH:48]=1)[CH2:40][CH2:41][CH3:42].CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>ClCCCl.C(Cl)Cl>[Br:1][C:2]1[N:7]=[C:6]([C:8](=[O:11])[NH:9][CH3:10])[C:5]([NH:12][C:13]2[C:18]([C:19]([F:22])([F:20])[F:21])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:36]=[CH:35][C:27]([CH2:28][P:29](=[O:33])([O:34][CH2:51][CH2:50][CH2:49][N:47]4[CH:48]=[C:44]([Sn:43]([CH2:53][CH2:54][CH2:55][CH3:56])([CH2:39][CH2:40][CH2:41][CH3:42])[CH2:57][CH2:58][CH2:59][CH3:60])[N:45]=[N:46]4)[O:30][CH2:31][CH3:32])=[CH:26][C:25]=3[O:37][CH3:38])[N:14]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 678145653-[4-(tributylstannanyl)-1H-1,2,3-triazol-1-yl]propan-1-ol2×HCID 86697762Ethyl hydrogen (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate2×

Product 1

HCID 86697832ethyl 3-[4-(tributylstannanyl)-1H-1,2,3-triazol-1-yl]propyl (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of ethyl hydrogen (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 38C, 205 mg, 0.331 mmol), 3-[4-(tributylstannanyl)-1H-1,2,3-triazol-1-yl]propan-1-ol (Compound 64B, 165 mg, 0.397 mmol) and DIPEA (0.17 mL, 0.993 mmol) in 1,2-dichloroethane (8 mL) was added (benzotriazol-1-yloxy)tripyrrolidino-phosphonium hexafluorophosphate (517 mg, 0.993 mmol). The resulting mixture was stirred at rt overnight. The mixture was diluted with DCM (30 mL), washed with sat. aq. NaHCO3 (2×20 mL), brine (20 mL), and dried over anhydrous sodium sulfate. The solvents were evaporated under reduced pressure, and the residue was purified by silica gel chromatography (ISCO system: MeOH/DCM=0-3%) to give the desired product, which was used in the following step. MS (ESI): m/z 1018.86 [M+H]+. UPLC: tR=1.22 min (UPLC-SQD: very non-polar—2 min).

Workup

  1. washwashed with sat. aq. NaHCO3 (2×20 mL), brine (20 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. customThe solvents were evaporated under reduced pressure
  4. customthe residue was purified by silica gel chromatography (ISCO system: MeOH/DCM=0-3%)

Sources & evidence

ORD record
ord-a478425e7c694025b68c2e640544ce01
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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