Triethylamine → 3-[(1S,5R)-9-[[(4R)-4-(2-chloro-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-1,4-dihydropyrimidin-6-yl]methyl]-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl]-2,2-dimethyl-3-oxo-propanoic acid

HRID 1778495Notes

Reaction equation

HRID 1778495 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@H:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([CH2:19][N:20]2[CH:25]3[CH2:26][NH:27][CH2:28][CH:21]2[CH2:22][O:23][CH2:24]3)[NH:12][C:11]([C:29]2[S:30][CH:31]=[CH:32][N:33]=2)=[N:10]1.C[O:35][C:36]([C:38]1[C@H:39](C2C=CC(F)=CC=2Cl)N=C(C2SC=CN=2)N[C:43]=1CN1C2CN(C(=O)C)CC1COC2)=[O:37].CN([C:73]([O:77]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@H:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([CH2:19][N:20]2[C@@H:25]3[CH2:26][N:27]([C:73](=[O:77])[C:38]([CH3:43])([CH3:39])[C:36]([OH:35])=[O:37])[CH2:28][C@H:21]2[CH2:22][O:23][CH2:24]3)[NH:12][C:11]([C:29]2[S:30][CH:31]=[CH:32][N:33]=2)=[N:10]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86293080(R)-6-(7-acetyl-3-oxa-7,9-diaza-bicyclo[3.3.1]non-9-ylmethyl)-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl esterHCID 117700087(R)-4-(2-chloro-4-fluoro-phenyl)-6-(3-oxa-7,9-diaza-bicyclo[3.3.1]non-9-ylmethyl)-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester

Product 1

HCID 1177002223-[(1S,5R)-9-[[(4R)-4-(2-chloro-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-1,4-dihydropyrimidin-6-yl]methyl]-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl]-2,2-dimethyl-3-oxo-propanoic acidYield 18%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of methyl (4R)-4-(2-chloro-4-fluoro-phenyl)-6-(3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-ylmethyl)-2-thiazol-2-yl-1,4-dihydropyrimidine-5-carboxylate (50 mg, 0.1 mmol), 2,2-dimethylpropanedioic acid (prepared as shown in Example 15) (26.4 mg, 0.2 mmol), HATU (48 mg, 0.25 mmol) and triethyl-amine (0.09 mL, 0.625 mmol) in dichloromethane (5 mL). The mixture was stirred at 25° C. for 16 h, and then concentrated in vacuo. The resulting residue was purified by preparative HPLC to afford 10 mg of the title compound as a white powder (yield was 18%).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe resulting residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-729b906ec0614d33af818ef4a53ee43e
Source dataset
uspto-grants-2016_02
Patent number
US09266904B2

Reaction notes

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