Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → HCID 86675328, compound

HRID 625046Notes

Reaction equation

HRID 625046 reaction equation
Cl.Cl.[CH2:3]([CH:5]1[C:13]2[C:12]([N:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)=[N:11][CH:10]=[N:9][C:8]=2[CH2:7][S:6]1)[CH3:4].[C:20]([O:24][C:25]([NH:27][C@H:28]([CH2:32][C:33]1[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([F:40])[CH:34]=1)[C:29](O)=[O:30])=[O:26])([CH3:23])([CH3:22])[CH3:21].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.C(N(CC)CC)C>[Cl:39][C:36]1[CH:37]=[CH:38][C:33]([CH2:32][C@@H:28]([NH:27][C:25](=[O:26])[O:24][C:20]([CH3:21])([CH3:22])[CH3:23])[C:29]([N:17]2[CH2:16][CH2:15][N:14]([C:12]3[C:13]4[CH:5]([CH2:3][CH3:4])[S:6][CH2:7][C:8]=4[N:9]=[CH:10][N:11]=3)[CH2:19][CH2:18]2)=[O:30])=[CH:34][C:35]=1[F:40]

Participants

6

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67340403N-Boc-4-chloro-3-fluoro-D-phenylalanineHCID 67459944HCID 67459944, compound

Product 1

HCID 86675328HCID 86675328, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 5-ethyl-4-(piperazin-1-yl)-5,7-dihydrothieno[3,4-d]pyrimidine dihydrochloride (50 mg, 0.15 mmol) and (R)-2-(tert-butoxycarbonylamino)-3-(4-chloro-3-fluorophenyl)propanoic acid (49 mg, 0.15 mmol) in DCM (10 mL) and triethylamine (1 mL) was added HBTU (59 mg, 0.15 mmol). The mixture was stirred at room temperature for 3 hours. The solvent was removed and the residue was purified by silica gel chromatography, eluting with DCM/ethyl acetate (1:1) to give tert-butyl (R)-3-(4-chloro-3-fluorophenyl)-1-(4-(5-ethyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-1-oxopropan-2-ylcarbamate (80 mg, 90%). 1H NMR (CDCl3, 400 MHz) δ 8.54 (s, 1H), 7.40-6.90 (m, 3H), 5.36 (m, 1H), 4.82 (m, 1H), 4.65 (m, 1H), 4.12 (m, 1H), 3.90-3.18 (m, 8H), 3.04-2.89 (m, 2H). 1.95 (m, 1H), 1.57 (m, 1H), 1.42 (s, 9H), 0.94 (m, 3H). MS (APCI+) [M+H]+ 551.

Workup

  1. customThe solvent was removed
  2. customthe residue was purified by silica gel chromatography
  3. washeluting with DCM/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-466bed8b0ac14b819b6a4e6a4c6df5de
Source dataset
uspto-grants-2016_04
Patent number
US09303040B2

Reaction notes

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