Water → HCID 178458734, compound

HRID 2200795Notes

Reaction equation

HRID 2200795 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[OH:8][C:9]([C:12]1[N:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:15]=[C:14]([O:22][C@@H:23]2[CH2:28][CH2:27][C@H:26]([N:29]3[CH2:32][C:31]([CH2:55][C:56]#[N:57])([N:33]4[CH:37]=[C:36]([C:38]5[C:39]6[CH:46]=[CH:45][N:44](COCC[Si](C)(C)C)[C:40]=6[N:41]=[CH:42][N:43]=5)[CH:35]=[N:34]4)[CH2:30]3)[CH2:25][CH2:24]2)[CH:13]=1)([CH3:11])[CH3:10].[OH-].[NH4+].O>CC#N.O.C(Cl)Cl>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[OH:8][C:9]([C:12]1[N:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:15]=[C:14]([O:22][C@@H:23]2[CH2:24][CH2:25][C@H:26]([N:29]3[CH2:32][C:31]([CH2:55][C:56]#[N:57])([N:33]4[CH:37]=[C:36]([C:38]5[C:39]6[CH:46]=[CH:45][NH:44][C:40]=6[N:41]=[CH:42][N:43]=5)[CH:35]=[N:34]4)[CH2:30]3)[CH2:27][CH2:28]2)[CH:13]=1)([CH3:10])[CH3:11]

Participants

7

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 14923Ammonium HydroxideHCID 178458733HCID 178458733, compound

Product 1

HCID 178458734HCID 178458734, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

Methylene chloride (2.0 mL) and trifluoroacetic acid (0.40 mL, 5.2 mmol) were added to {1-(cis-4-{[6-(1-hydroxy-1-methylethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, stirred for 2 hours, and then concentrated to remove trifluoroacetic acids. LCMS showed clean conversion to the hydroxymethyl intermediate (M+2H 320). To the residue was added methanol (2.0 mL), then 15.0 M ammonium hydroxide in water (1.8 mL, 27 mmol). The solution was stirred 2.5 hours. LCMS showed the reaction was complete. The product was isolated by preparative LCMS using a Waters Fraction-Linx instrument and a 30 mm×100 mm Sunfire C18 column (5% CH3CN—H2O (0.1% TFA), 4.0 minutes; 8.0 min gradient to 30%; 60 mL/min; 8 runs; retention time 11.0 minutes). The eluent was concentrated by 50%, then freeze-dried to give white solid. 1H NMR (300 MHz, MeOH-D4): δ 8.99 (s, 1H); 8.82 (s, 1H); 8.57 (s, 1H); 7.71 (m, 1H); 7.20 (s, 1H); 7.16 (m, 1H); 5.48 (m, 1H, OCH); 5.06 (d, 2H azetidine) 4.8 (d, 2H, azetidine); 3.70 (s, 2H, CH2CN); 3.50 (m, 1H, NCH); 2.30 (m, 2H); 2.01 (m, 2H); 1.80 (m, 2H); 1.75 (m, 2H); 1.50 (s, 6H). MS: 582 (M+H)

Workup

  1. concentrationconcentrated
  2. customto remove trifluoroacetic acids
  3. additionTo the residue was added methanol (2.0 mL)
  4. stirringThe solution was stirred 2.5 hours
  5. customThe product was isolated by preparative LCMS
  6. concentrationThe eluent was concentrated by 50%
  7. customfreeze-dried
  8. customto give white solid

Sources & evidence

ORD record
ord-e4741a0223ac421da6f6bee4ffbf7a1e
Source dataset
uspto-grants-2016_06
Patent number
US09359358B2

Reaction notes

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